Antimicrobial material comprising synergistic combinations of metal oxides

ABSTRACT

The present invention relates to methods and articles for wound healing involving the use of a material having antimicrobial properties, said material comprising a synergistic combination of at least two metal oxide powders, comprising a mixed oxidation state oxide of a first metal and a single oxidation state oxide of a second metal, wherein the mixed oxidation state oxide constitutes from about 0.05% to about 15% wt. of the total weight of the synergistic combination of the at least two metal oxide powders and wherein the ions of the metal powders are in ionic contact upon exposure of said material to moisture.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is a Continuation-in-Part of U.S. application Ser. No.16/703,342, filed Dec. 4, 2019, which is a Continuation of U.S.application Ser. No. 15/549,018, filed Aug. 4, 2017, which is a NationalPhase Application of PCT/IL2015/050142, filed Feb. 8, 2015; the contentsof all of which are incorporated herein by reference in their entirety.

FIELD OF THE INVENTION

The present invention relates to materials comprising a polymer having asynergistic combination of metal oxides incorporated within the polymer,the materials having antimicrobial properties.

BACKGROUND OF THE INVENTION

It is widely known that crowded places (such as hospitals, healthcarefacilities, food processing plants, hotels, dormitories, and publictransportation) bear the potential risk of transferring diseases. Hencesuch places require use of products which are less prone to microbe andpathogen proliferation. As microbes evolve to be more pathogenic anddrug resistant, the need to keep the bio-burden levels under control hasincreased, and more effective avenues of control need to be developed.

On many hospital items and equipment the presence of microorganisms inthe hospital environment can lead to healthcare associated infections(HAIs). Even with all present-day cleaning and disinfection solutions,in the United States 4.5% of hospitalized patients develop HAI,resulting in an estimated 100,000 deaths annually and adding 35.7 to 45billion dollars to healthcare costs. Bacteria and other microorganismscan evade routine cleaning which cannot provide long term protectionagainst microorganisms. What is needed is a fast-acting, continuous (notepisodic) supplement to conventional cleaning. It should also beinexpensive without compromising on efficacy, as healthcare institutionshave very tight budgets.

It has previously been shown that certain individual metal oxides, whenexposed to moisture, will release ions to the environment in which themetal oxide is exposed. It is also known that these ions haveantimicrobial, antiviral, and anti-fungal properties (Borkow and Gabbay,FASEB J. 2004 November; 18(14):1728-30), as well as anti-mite qualities(Mumchuoglu, Gabbay, Borkow, International Journal of Pest Management,Vol. 54, No. 3, July-September 2008, 235-240).

U.S. Pat. No. 6,124,221 discloses an article of clothing havingantibacterial, antifungal, and anti-yeast properties, comprising atleast a panel of a metalized textile, said textile including fibersselected from the group consisting of natural fibers, syntheticcellulosic fibers, regenerated protein fibers, acrylic fibers,polyolefin fibers, polyurethane fibers, vinyl fibers, and blendsthereof, and having a plating including an antibacterial, antifungal andanti-yeast effective amount of at least one oxidant cationic species ofcopper wherein the plating is bonded directly to the fibers.

U.S. Pat. No. 6,482,424 discloses a method for combating and preventingnosocomial infections, comprising providing to health care facilitiestextile fabrics incorporating fibers coated with an oxidant, cationicform of copper, for use in patient contact and care, wherein the textilefabric is effective for the inactivation of antibiotic resistant strainsof bacteria.

U.S. Pat. No. 7,169,402 encompasses antimicrobial and antiviralpolymeric materials, comprising a polymer selected from the groupconsisting of polyamide, polyester, and polypropylene, and a singleantimicrobial and antiviral component consisting essentially ofmicroscopic water insoluble particles of copper oxide incorporated inthe polymer, wherein a portion of said particles in said polymer areexposed and protruding from the surface of the material, and whereinsaid particles release Cu²⁺ when exposed to water or water vapor.

US Patent Application Publication No. 2008/0193496 discloses polymericmaster batch for preparing an antimicrobial and antifungal and antiviralpolymeric material comprising a slurry of thermoplastic resin, anantimicrobial and antifungal and antiviral agent consisting essentiallyof water insoluble particles of ionic copper oxide, a polymeric wax andan agent for occupying the charge of said ionic copper oxide.

U.S. Pat. No. 7,364,756 discloses a method for imparting antiviralproperties to a hydrophilic polymeric material comprising preparing ahydrophilic polymeric slurry, dispersing an ionic copper powder mixturecontaining cuprous oxide and cupric oxide in said slurry and thenextruding or molding said slurry to form a hydrophilic polymericmaterial, wherein water-insoluble particles that release both Cu⁺⁺ andCu⁺ are directly and completely encapsulated within said hydrophilicpolymeric material.

Similar findings on antimicrobial activity of metal oxides have alsobeen published in connection to tetrasilver tetroxide as a mixedoxidation state compound as cited in various publications and patents byAntelman.

U.S. Pat. No. 6,645,531 to Antelman discloses pharmaceuticalcompositions that include a therapeutically effective amount of at leastone electron active compound, or a pharmaceutically acceptablederivative thereof, that has at least two polyvalent cations, at leastone of which has a first valence state and at least one of which has asecond, different valence state. Preferred compounds include Bi(III,V)oxide, Co(II,III) oxide, Cu(I,III) oxide, Fe(II,III) oxide, Mn(II,III)oxide, and Pr(III,IV) oxide, and optionally Ag(I,III) oxide. Furtherprovided are methods of halting, diminishing, or inhibiting the growthof at least one of a bacterium, a fungus; a parasitic microbe, and avirus, comprising administering to a human subject a therapeuticallyeffective amount of the at least one electron active compound.

U.S. Pat. No. 6,436,420 to Antelman is related to fibrous textilearticles possessing enhanced antimicrobial properties prepared by thedeposition or interstitial precipitation of tetrasilver tetroxide(Ag₄O₄) crystals within the interstices of fibers, yarns and/or fabricsforming such articles.

There is an unmet need for a cost-effective material having improvedantimicrobial and antiviral properties, which can be beneficially usedin combating or inhibiting microbe activity and preventing or treatinginfections.

SUMMARY OF THE INVENTION

The present invention relates to materials having antimicrobialproperties and methods for the preparation thereof. The antimicrobialmaterial comprises a polymer and a synergistic combination of at leasttwo metal oxide powders incorporated within the polymer, comprising amixed oxidation state oxide and a single oxidation state oxide. Themetal oxide powders are incorporated within the polymer such that uponhydration of the material, the ions of the two metal oxides are in ioniccontact with each other.

The present invention is based in part on an unexpected discovery thatthe antimicrobial activity of a single oxidation state metal oxide isenhanced by the addition of a mixed oxidation state metal oxide, whereinthe two metal ions are in ionic contact, such that the combination ofthe metal oxide particles provides a synergistic effect as compared tothe activity of each of the metal oxides alone. It has further beensurprisingly found that even the addition of the mixed oxidation stateoxide in an amount of less than 10% wt. of the total weight of thecombination provides synergistic antimicrobial effect. Additionally, ithas been surprisingly found that the synergistic combination of themixed oxidation state metal oxide and the single oxidation state metaloxide was particularly efficient in wound healing, even when usingrelatively low concentration of the mixed oxidation state metal oxide(e.g., less than 15% wt., less than 10% wt., less than 5% wt., or evenless than 1% wt. out of the total weight of the combination).

Homogeneous incorporation of inorganic particles into a substrate,particularly a polymeric substrate, is challenged by particleagglomeration, chemical and physical interaction between the particlesand the substrate and most of all by difference in the specificgravities of the particulate materials. However, materials of thepresent invention, which in some embodiments comprise particulate metaloxides having substantially different specific gravities, are generallycharacterized by a homogeneous distribution of the metal oxide powderswithin the polymer fiber. The present invention overcomes the problemimposed by use of distinct types of metal oxides by equalizing bulkdensities of the metal oxide particles. Thus, according to someembodiments, the materials of the present invention comprise metal oxidepowders, which, even though having substantially different specificgravities, have substantially similar bulk densities. Mean particlesizes of the metal oxides can be proportionally reduced in order tocompensate for the difference in the specific gravities thereof andobtain substantially similar bulk densities. Alternatively, bulkdensities of the metal oxides can be equalized by coating the metaloxide powders with a coating, which thickness or weigh is proportionalto the specific gravity of the powders.

According to one aspect, the present invention provides a materialhaving antimicrobial properties, said material comprising a polymerhaving incorporated therein synergistic combination of at least twometal oxides comprising a mixed oxidation state oxide of a first metaland a single oxidation state oxide of a second metal, the powders beingincorporated substantially uniformly within said polymer, wherein thepowders have substantially different specific gravities andsubstantially similar bulk densities, and wherein the ions of the metaloxides are in ionic contact upon exposure of said material to moisture.According to some embodiments, the first metal and the second metal aredifferent.

According to another aspect, the present invention provides a method oftreating a wound, comprising applying to the wound a material havingantimicrobial properties, said material comprising a synergisticcombination of at least two metal oxide powders, comprising a mixedoxidation state oxide of a first metal and a single oxidation stateoxide of a second metal, wherein the mixed oxidation state oxideconstitutes from about 0.05% to about 15% wt. of the total weight of thesynergistic combination of the at least two metal oxide powders andwherein the ions of the metal oxides are in ionic contact upon exposureof said material to moisture.

In another embodiments, the present invention provides a wound healingarticle comprising a material having antimicrobial properties, saidmaterial comprising a synergistic combination of at least two metaloxide powders, comprising a mixed oxidation state oxide of a first metaland a single oxidation state oxide of a second metal, wherein the mixedoxidation state oxide constitutes from about 0.05% to about 15% wt. ofthe total weight of the synergistic combination of the at least twometal oxide powders and wherein the ions of the metal oxides are inionic contact upon exposure of said material to moisture.

According to some embodiments, treating the wound comprises at least oneof wound healing, accelerated wound closure, and wound healing withreduced scarring.

In some embodiments, the mixed oxidation state oxide is selected fromthe group consisting of tetrasilver tetroxide (Ag₄O₄), Ag₃O₄, Ag₂O₂,tetracopper tetroxide (Cu₄O₄), Cu (I,III) oxide, Cu (II,III) oxide,Cu₄O₃ and combinations thereof. Each possibility represents a separateembodiment of the invention. In further embodiments, the mixed oxidationstate oxide is selected from the group consisting of tetrasilvertetroxide (Ag₄O₄), Ag₂O₂, tetracopper tetroxide (Cu₄O₄), Cu (I,III)oxide, Cu (II,III) oxide and combinations thereof. Each possibilityrepresents a separate embodiment of the invention. In some embodiments,the single oxidation state oxide is selected from the group consistingof copper oxide, silver oxide, zinc oxide and combinations thereof. Eachpossibility represents a separate embodiment of the invention. Copperoxide may be selected from the group consisting of cuprous oxide (Cu₂O),cupric oxide (CuO) and combinations thereof. Each possibility representsa separate embodiment of the invention. In particular embodiments, thecombination of the at least two metal oxides comprises copper oxide andtetrasilver tetroxide. In further particular embodiments, copper oxideis cuprous oxide.

According to some embodiments, the mixed oxidation state oxideconstitutes up to about 60% wt. of the total weight of the synergisticcombination of the at least two metal oxide powders. According tofurther embodiments, the mixed oxidation state oxide constitutes up toabout 15% wt. of the total weight of the synergistic combination of theat least two metal oxide powders.

According to some embodiments, the mixed oxidation state oxideconstitutes from about 0.05% to about 10% wt. of the total weight of thesynergistic combination of the at least two metal oxide powders.According to further embodiments, the mixed oxidation state oxideconstitutes from about 0.05% to about 5% wt. of the total weight of thesynergistic combination of the at least two metal oxide powders.According to still further embodiments, the mixed oxidation state oxideconstitutes from about 0.05% to about 1% wt. of the total weight of thesynergistic combination of the at least two metal oxide powders.According to yet further embodiments, the mixed oxidation state oxideconstitutes from about 0.05% to about 0.5% wt. of the total weight ofthe synergistic combination of the at least two metal oxide powders.According to still further embodiments, the mixed oxidation state oxideconstitutes from about 0.05% to about 0.25% wt. of the total weight ofthe synergistic combination of the at least two metal oxide powders.According to additional embodiments, the mixed oxidation state oxideconstitutes from about 0.5% to about 15% wt. of the total weight of thesynergistic combination of the at least two metal oxide powders.According to yet further embodiments, the mixed oxidation state oxideconstitutes about 1% wt. of the total weight of the synergisticcombination of the at least two metal oxide powders.

According to some embodiments, the mixed oxidation state oxideconstitutes from about 0.05% to about 15% wt. of the total weight of thesynergistic combination of the at least two metal oxide powders.According to further embodiments, the mixed oxidation state oxide ispresent in the synergistic combination of the at least two metal oxidepowders in a detectable amount. According to still further embodiments,the presence of the mixed oxidation state oxide in the material isdetectable by means of an X-ray diffraction spectroscopy (XRD), electronmicroscopy, electron spectroscopy, Raman spectroscopy orelectoanalytical methods. Each possibility represents a separateembodiment of the invention.

According to some embodiments, the metal oxides are not exposed on thesurface of the material. According to other embodiments, the powders aredistributed on the surface of the material in a generally uniformfashion. According to further embodiments, the metal oxide particlesprotrude from a surface of the material. In yet further embodiments, themetal oxide particles are attached to, deposited on or inserted into thesurface of the material.

According to some embodiments, each of the metal oxide powdersindependently comprises particles, having a mean particle size of fromabout 1 nanometer to about 10 microns. According to other embodiments,each of the metal oxide powders independently comprises particles, whichsize is from about 10 nanometers to about 10 microns. According tofurther embodiments, each of the metal oxide powders independentlycomprises particles, which size is from about 0.5 to about 1.5 microns.

According to some embodiments, the metal oxide powders havesubstantially similar bulk densities. According to some embodiments, themetal oxide powders having the substantially similar bulk densitiescomprise particles which mean particle size is inversely proportional tothe specific gravity thereof. According to other embodiments, the metaloxide powders having the substantially similar bulk densities compriseparticles which have substantially similar mean particles sizes andwherein said particles are coated with a coating. According to furtherembodiments, the coating thickness is proportional to the specificgravity of the metal oxide particles. In alternative embodiments, thecoating weight is proportional to the specific gravity of the metaloxide powders. According to further embodiments, the coating comprisespolyester or polyalkene wax. The polyester or polyalkene wax may beselected from the group consisting of a polypropylene wax, oxidizedpolyethylene wax, ethylene homopolymer wax and a combination thereof.Each possibility represents a separate embodiment of the invention.

According to further embodiments, the metal oxide powders compriseparticles, which are encapsulated within an encapsulating compound. Theencapsulating compound may comprise silicate, acrylate, cellulose,derivatives thereof or combinations thereof. The non-limiting example ofacrylate is poly(methyl methacrylate) (PMMA). According to someexemplary embodiments, the encapsulating agent is a silicate or apoly(methyl methacrylate) (PMMA).

According to some embodiments, the material of the present inventionfurther comprises a chelating agent or a metal deactivating agentassociated with the metal oxide powders. The metal deactivating agentmay be selected from the group consisting of phenolic antioxidant,potassium iodide, potassium bromide, calcium stearate, zinc stearate,aluminum stearate, tertiary chain extender and a combination thereof.Each possibility represents a separate embodiment of the invention.

According to further embodiments, the material of the present inventionfurther comprises a surfactant associated with the metal oxide powder.The surfactant may include a sulfate, a sulfonate, a silicone, a silane,or a non-ionic surfactant. The non-limiting examples of commerciallyavailable surfactants include Sigma Aldrich Niaproof®, Dow CorningXiameter® and Triton-X-100. The surfactant may further comprise asolvent, such as but not limited to, methyl alcohol, methyl ethylketone, or toluene. According to some embodiments, the material isdevoid of the surfactant.

According to some embodiments, the material comprises a polymericmaterial having incorporated therein the synergistic combination of atleast two metal oxide powders. According to some embodiments, thepolymer is selected from a synthetic polymer, naturally occurringpolymer or combinations thereof. Each possibility represents a separateembodiment of the invention. According to some embodiments, thesynthetic polymer is selected from the group consisting of organicpolymers, inorganic polymers and bioplastics. In further embodiments,the polymer is selected from the group consisting of polyamide,polyester, acrylic, polyalkene, polysiloxane, nitrile, polyvinylacetate, starch-based polymer, cellulose-based polymer, dispersions andmixtures thereof. According to some currently preferred embodiments, thepolymer is selected from polyester, polyalkene and polyamide. Thepolyalkene may be selected from the group consisting of polypropylene,polyethylene and combinations thereof. Each possibility represents aseparate embodiment of the invention. According to particularembodiments, the polymer is selected from polyethylene, polypropylene,acrylonitrile butadiene styrene (ABS), polylactic acid (PLA),polyglycolic acid (PGA), poly(lactic-co-glycolic acid) (PLGA),poly(butyl acrylate) (PBA), polybutylene terephthalate (PBT) andcombinations thereof. The polymer may be water based or solvent based.

According to various embodiments, the material is incorporated into awound healing article. The wound healing article can be selected fromthe group consisting of a gauze, gauze pad, wound covering, trans-dermalpatch, bandage, adhesive bandage disposable sanitary product, suture,and article of clothing that can come in contact with a wound.

According to some embodiments, the material of the present invention isselected from an intermediate-product, a semi-final product or a finalproduct.

In some embodiments, the metal oxide powders are incorporated into thepolymer by means of a master batch manufacturing process. Thus,according to some embodiments, the intermediate product is amaster-batch.

According to some embodiments, the semi-final product comprises a fiber,a yarn, a textile, a fabric, a film or a foil. Each possibilityrepresents a separate embodiment of the invention. The textile can beselected from a woven textile, a knit textile, a non-woven textile, aneedle-punch textile or felt. Each possibility represents a separateembodiment of the invention. According to certain embodiments, thesemi-final product is a fiber. The fiber can be a filament fiber or astaple fiber. According to some embodiments, the metal oxide powders areincorporated substantially uniformly within the fiber. The fiber can beformed into a yarn, textile or fabric.

According to some embodiments, the final product is a textile product ora non-textile polymeric article. According to some embodiments, theyarn, textile or fabric are formed into the textile product.

According to further embodiments, the polymer is formed into asemi-final product or a final product by means of extrusion, molding,casting or 3D printing. Each possibility represents a separateembodiment of the invention. According to some embodiments, the textileproduct comprises an extruded polymer. According to further embodiments,the semi-final product comprises an extruded polymer. According tocertain embodiments, the fiber comprises an extruded polymer. Accordingto additional embodiments, the non-textile polymeric article comprisesan extruded, molded or cast polymer.

In some embodiments, the combined weight of the at least two metaloxides constitutes from about 0.25% to about 50% wt. of the total weightof the material.

In some embodiments, the material is in a form of a master batch. Infurther embodiments, the combined weight of the at least two metaloxides constitutes from about 0.5% to about 50% wt. of the total weightof the master batch. In yet further embodiments, the combined weight ofthe at least two metal oxides constitutes from about 20% to about 40%wt. of the total weight of the master batch.

In some embodiments, the material is in a form of a fiber, a yarn, atextile or a fabric. In certain such embodiments, the combined weight ofthe at least two metal oxides constitutes from about 0.5% to about 15%wt. of the total weight of the material.

According to some embodiments, the fiber is a polymeric fiber, beingsynthetic or semi-synthetic. According to some embodiments, the materialfurther comprises a natural fiber. Thus, in some embodiments, the fiberis a blend of the polymeric fiber with a natural fiber.

According to further embodiments, the material comprises natural fiberis a weight percent of up to about 85% of the total weight of thematerial. In particular embodiments, the material comprises naturalfiber is a weight percent of up to about 70% of the total weight of thetextile product. The natural fiber may be selected from the groupconsisting of cotton, silk, wool, linen and combinations thereof. Eachpossibility represents a separate embodiment of the invention. In acertain embodiment, the material comprises cotton.

According to some embodiments, the material comprises the blend of apolymeric fiber and a natural fiber. In certain such embodiments, thecombined weight of the at least two metal oxides constitutes from about0.25% to about 5% wt. of the total weight of the material.

According to some embodiments, the material is in a form of a textileproduct or a non-textile polymeric article. Each possibility representsa separate embodiment of the invention. The textile product may beselected from clothing items, bedding textiles, laboratory or hospitaltextiles, medical textiles including bandages or sutures and textilesfor internal use, or personal hygiene articles. The non-limitingexamples of the textile products include pillowcases, eye-masks, gloves,socks, stockings, sleeves, shoe covers, slippers, undergarments,industrial uniforms, sportswear, towels, kitchen cloths, lab coats,floor cloths, sheets, bedding, curtains, textile covers, hard surfacecovers, diapers, incontinence pads, feminine hygiene products, gauzepads, monolithic extruded membranes, body-suits, trans-dermal patches,bandages, adhesive bandages, sutures, sheaths and textiles for internaluse. The non-textile polymeric article may be selected from packaging orwrapping material, laboratory equipment, hospital equipment, preferablydisposable hospital equipment, birth-control devices, agriculturalproducts, covers for consumer items, and sanitary products. Thenon-limiting examples of the non-textile polymeric articles include foodpackages, gloves, blood bags, catheters, ventilation tubes, feedingtubes, transmission tubes, covers for mobile phones, pipes, toilet seatsor toilet seat covers, kitchen sponges, working surface covers, andcondoms. In certain embodiments, the material is in a form of a productselected from the group consisting of clothing items, bedding textiles,laboratory or hospital textiles, laboratory equipment, hospitalequipment, medical textiles including bandages or sutures and textilesfor internal use, personal hygiene articles, packaging or wrappingmaterial, covers for consumer items, food equipment, birth-controldevices, agricultural products, or sanitary products.

In some embodiments, the present invention provides the material for usein combating or inhibiting the activity of microbes or micro-organisms,selected from the group consisting of gram-positive bacteria,gram-negative bacteria, fungi, parasites, mold, spores, yeasts,protozoa, algae, acarii and viruses. Each possibility represents aseparate embodiment of the invention.

According to some embodiments, the material is for use in combatinghealthcare associated infections, nosocomial infections or a combinationthereof. Each possibility represents a separate embodiment of theinvention.

Alternatively or additionally, the material of the present invention canbe used for the treatment or prevention of atopic fungal, bacterial andviral infections. The infection may be selected from the groupconsisting of athlete's foot, yeast infections and staph infections.Each possibility represents a separate embodiment of the invention. Infurther embodiments, the material is for use in the treatment orprevention of topical viral infections. The infection may be selectedfrom the group consisting of warts and Herpes B. Each possibilityrepresents a separate embodiment of the invention.

In another aspect, the present invention provides a method for thepreparation of a material having antimicrobial properties, said materialcomprising a polymer having incorporated therein a synergisticcombination of at least two metal oxide powders, comprising a mixedoxidation state oxide of a first metal and a single oxidation stateoxide of a second metal, the powders being incorporated substantiallyuniformly within said polymer, wherein the powders have substantiallydifferent specific gravities and substantially similar bulk densities,and wherein the ions of the metal oxides are in ionic contact uponexposure of said material to moisture, the method comprising the stepsof:

-   -   a. processing the at least two metal oxide powders to have        substantially similar bulk densities; and    -   b. mixing said powders with at least one polymer.

According to some embodiments, step a. comprises processing the metaloxide powders to obtain particles having mean particles sizes which areinversely proportional to the specific gravity thereof. In someembodiments, said processing comprises grinding.

According to other embodiments, step a. comprises processing the metaloxide powders to obtain particles having substantially similar sizes. Insome embodiments, said processing comprises grinding. In additionalembodiments, step a. further comprises applying a coating to the metaloxide powder particles. In some embodiments, step a. comprises applyinga coating to the particles of at least one of the metal oxide powders.In further embodiments, step a. comprises applying a coating to theparticles of each of the at least two metal oxide powders. In furtherembodiments, the coating thickness is proportional to the specificgravity of the metal oxide powders.

In some embodiments, the method further comprises a step ofencapsulating the metal oxide powder particles within an encapsulatingcompound. In other embodiments, the method comprises a step of mixingthe metal oxide powders with a metal deactivating agent or a chelatingagent. In further embodiments, the method comprises a step of mixing themetal oxide powders with a surfactant.

According to further embodiments, step b. comprises producing a masterbatch, comprising the metal oxide powders and a carrier polymer.According to some embodiments, said at least one polymer comprises thecarrier polymer. According to the preferred embodiments, the masterbatch is homogeneous. The master batch may be formed into pellets.Alternatively, the master batch may be formed into granules.

In some embodiments step b. further comprises adding the master batch toa polymer slurry. In further embodiments the polymer slurry comprises apolymer, which is the same as the carrier polymer. In other embodiments,the polymer slurry comprises a polymer, which is chemically compatiblewith the carrier polymer.

According to some embodiments, the method further comprises step c.comprising forming from the obtained mixture a film, a foil, a fiber, ayarn, a fiber, a textile, a textile product or a non-textile polymericarticle. Each possibility represents a separate embodiment of theinvention.

According to some particular embodiments, the method further comprisesstep c. comprising forming from the obtained mixture a film, a foil, afiber, a yarn, a fiber or a textile, comprising said powders. Eachpossibility represents a separate embodiment of the invention. Accordingto other particular embodiments, the method further comprises step c.,comprising forming from the obtained mixture a textile product or anon-textile polymeric article, comprising said powders. Each possibilityrepresents a separate embodiment of the invention.

In some embodiments, step c. comprises extrusion, molding, casting or 3Dprinting. In some exemplary embodiments step c. comprises extrusion. Infurther embodiments, extrusion comprises spinning through a spinneret.In the preferred embodiments, the material is homogeneously extruded. Inother embodiments step c. comprises molding.

In some embodiments, step c. comprises forming a polymeric fiber fromthe mixture obtained in step b. In some embodiments, the method furthercomprises blending the polymer fiber with a natural fiber. In someembodiments, the method comprises forming the fiber into yarn, textile,fabric or a textile product.

Further embodiments and the full scope of applicability of the presentinvention will become apparent from the detailed description givenhereinafter. However, it should be understood that the detaileddescription and specific examples, while indicating preferredembodiments of the invention, are given by way of illustration only,since various changes and modifications within the spirit and scope ofthe invention will become apparent to those skilled in the art from thisdetailed description.

BRIEF DESCRIPTION OF THE FIGURES

FIG. 1A: SEM micrograph of a polyester staple fiber containing copperoxide and tetrasilver tetroxide, prepared by a master batch preparationmethod, at 1000× magnification with protruding particles.

FIG. 1B: SEM micrograph of a polyester staple fiber containing copperoxide and tetrasilver tetroxide, prepared by a master batch preparationmethod, at 4000× magnification with protruding particles.

FIG. 1C: SEM micrograph of a cross section of the fiber of FIGS. 1A and1B, showing copper oxide and tetrasilver tetroxide at 4000×magnification with protruding particles.

FIG. 2A: SEM micrograph of a cotton fiber with sonochemicallynano-deposited copper oxide impregnated with tetrasilver tetroxide at5000× magnification.

FIG. 2B: SEM micrograph of a cotton fiber with sonochemicallynano-deposited copper oxide impregnated with tetrasilver tetroxide at20000× magnification.

FIG. 3: SEM micrograph of a polyester staple fiber impregnated withcopper oxide and tetrasilver tetroxide, via a sonication assistedprocess, at 20000× magnification with particles enclosed within thefiber.

FIG. 4: Bacteria proliferation inhibition of the extruded polypropylenefilm comprising copper oxide and tetrasilver tetroxide (dashed line) ascompared to the control (solid line), which is untreated polypropylenefilm of the same material and size.

FIGS. 5A-5C: Bacteria proliferation inhibition of the polymeric fabriccomprising copper oxide and tetrasilver tetroxide, wherein solid colorbars represent a polymeric fabric comprising a combination of copperoxide and TST, and confetti pattern bars represent control—untreatedfabric of the same material and size. FIG. 5A—Bacteria proliferationinhibition between 0 and 40 minutes from the exposure of the fabric tothe bacteria containing medium, FIG. 5B—Bacteria proliferationinhibition between 0 and 180 minutes from the exposure of the fabric tothe bacteria containing medium, FIG. 5C—Bacteria proliferationinhibition between 0 and 300 minutes from the exposure of the fabric tothe bacteria containing medium.

FIG. 6A-6B: Bacteria proliferation inhibition of the polymeric fabriccomprising copper oxide, wherein grid pattern bars represent a polymericfabric comprising copper oxide, and dotted pattern bars representcontrol—untreated fabric of the same material and size. FIG. 6A—Bacteriaproliferation inhibition between 0 and 40 minutes from the exposure ofthe fabric to the bacteria containing medium, and FIG. 6B—Bacteriaproliferation inhibition between 0 and 180 minutes from the exposure ofthe fabric to the bacteria containing medium.

FIG. 7: Bacteria proliferation inhibition of the cotton blend polymericfabrics comprising copper oxide and tetrasilver tetroxide and copperoxide alone, wherein stripes patter bars represent an untreated control(70% cotton/30% polyester fiber), checker board pattern bars represent70% cotton/30% polyester fiber containing copper oxide, grid patternbars represent 50% cotton/50% polyester fiber containing a combinationof copper oxide and TST, and solid color bars represent 70% cotton/30%polyester fiber containing a combination of copper oxide and TST.

DETAILED DESCRIPTION

The present invention relates to materials having improved antimicrobialproperties, including increased antibacterial, antiviral andantiparasitic activity, and to methods for preparation of saidmaterials. The antimicrobial materials of the present invention comprisea polymer and a synergistic combination of at least two metal oxidepowders homogeneously incorporated into said polymer.

As used herein, the term “antimicrobial” refers to an inhibiting,microcidal or oligodynamic effect against microbes, pathogens, andmicroorganisms, including but not limited to enveloped viruses,non-enveloped viruses, gram-positive bacteria, gram-negative bacteria,fungi, parasites, mold, yeasts, spores, algae, protozoa, acarii and dustmites, amongst others, and subsequent anti-odor properties.

According to some embodiments, the material of the present invention isselected from an intermediate-product, such as, but not limited to, amaster batch; a semi-final product, for example, a fiber, a yarn, atextile, a fabric, a film or a foil; or a final product, including,inter alia, a textile product or a non-textile polymeric article.

The synergistic combination of the at least two metal oxide powderscomprises a mixed oxidation state oxide of a first metal and a singleoxidation state oxide of a second metal, wherein the powders havesubstantially similar bulk densities and wherein the ions of the metaloxides are in an ionic contact upon hydration of said material or itsexposure to residual moisture.

As used herein, the term “ionic contact” refers to the ability of ionsof each of the metal oxide powders, being incorporated within thepolymer, to flow to a mutual aqueous reservoir upon exposure to saidreservoir.

The Synergistic Combination of Two Metal Oxides

It has been surprisingly found that in order to improve antimicrobialproperties of a single oxidation state metal oxide, a mixed oxidationstate metal oxide compound should be added to the single oxidation stateoxide. Without wishing to being bound by theory or mechanism of action,in order to provide the induced biocidal activity, the metal oxideparticles should be mixed together in such a manner that the particlesof each oxide are exposed to the same moisture reservoir, thus enablinga diffusion of ions from each metal oxide compound to the mutualmoisture reservoir.

The synergistic combination of the two metal oxides, wherein at leastone of the metal oxides is a mixed oxidation state oxide and at leastone of the metal oxides is a single oxidation state oxide is anon-naturally occurring biologically active combination. According tosome embodiments, said non-naturally occurring combination of metaloxides applied to a polymer substrate demonstrates greater ionicactivity than the naturally occurring compounds alone. Without wishingto being bound by theory or mechanism of action, the increased ionicactivity is responsible for a greater microcidal effect when compared tothe equal amounts of naturally occurring metal oxide compounds undersimilar conditions.

As defined herein, the term “synergistic combination” refers to acombination of at least two metal oxides, which provides higherantimicrobial efficiency than the equal amount of each of the metaloxides alone. The higher antimicrobial efficiency may relate toaccelerated bacteria or micro-organism killing rate.

The synergistic combination applied to a polymer comprises two or morebiologically active relatively insoluble metal oxides, wherein at leastone metal oxide is selected from single oxidation state oxide compounds,and at least one metal oxide is selected from mixed oxidation stateoxide compounds has been found to be biologically active by itself andsynergistic, providing surprisingly accelerated microbe mortality ascompared to the same single and mixed oxidation state metal oxidesindividually, or combined within the single oxidation state group whichare naturally occurring.

As used herein, the term “mixed oxidation state” refers to atoms, ionsor molecules in which the electrons are to some extent delocalized viavarious electronic transition mechanisms and are shared amongst theatoms, creating a conjugated bond which affects the physiochemicalproperties of the material. In the mixed oxidation state, electronictransitions form a superposition between two single oxidation states.This can be expressed as any metal that has more than a single oxidationstate coexisting, as in the formula X (Y, Z), where X is the metalelement and Y and Z are the oxidation states, where Y≠Z. The mixedoxidation state oxide may be one compound, wherein metal ions are indifferent oxidation states (i.e. X(Y,Z)).

According to some embodiments, the mixed oxidation state oxide useful inthe materials of the present invention is selected from the groupconsisting of tetrasilver tetroxide (TST)—Ag₄O₄ (Ag I, III), Ag₃O₄,Ag₂O₂, tetracopper tetroxide—Cu₄O₄ (Cu I, III), Cu₄O₃, Cu (I, II), Cu(II, III), Co(II,III), Pr(III,IV), Bi(III,V), Fe(II,III), and Mn(II,III)oxides and combinations thereof. Each possibility represents a separateembodiment of the invention. In certain embodiments, the materialcomprises a mixed oxidation state oxide selected from the groupconsisting of tetrasilver tetroxide, tetracopper tetroxide and acombination thereof.

As used herein, the term “single oxidation state” refers to atoms, ionsor molecules in which same types of atoms are present in one oxidationstate only. For example, in copper (I) oxide copper all ions are in theoxidation state +1, in copper (II) oxide all copper ions are in theoxidation state +2 and in zinc oxide all zinc ions are in oxidationstate +2.

According to some embodiments, the single oxidation state oxide usefulin the materials of the present invention is selected from the groupconsisting of copper oxide, silver oxide, zinc oxide and combinationsthereof.

As used herein, the term “copper oxide” refers to either or both ofcopper oxide's multiple oxidation states: the first, principal singleoxidation state cuprous oxide ((Cu₂O), also identified as copper (I)oxide); or the second, higher single oxidation state cupric oxide((CuO), also identified as copper (II) oxide) either individually or invarying proportions of the two naturally occurring oxidation states.

As used herein, the term “silver oxide” refers to silver oxide'smultiple oxidation states: the first, principal single oxidation stateAg₂O (also identified as silver (I) oxide); or the second, higher singleoxidation state AgO, (also identified as silver (II) oxide); or thethird highest single oxidation state Ag₂O₃, individually or in anyvarying proportion of these three naturally occurring oxidation states.

As used herein, the term “zinc oxide” refers to zinc oxide's principaloxidation state ZnO₂.

According to some embodiments, copper oxide is selected from the groupconsisting of Cu₂O, CuO and combinations thereof. According to furtherembodiments, silver oxide is selected from the group consisting of Ag₂O,AgO, Ag₂O₃ and combinations thereof. Each possibility represents aseparate embodiment of the invention.

In certain embodiments, the material comprises a single oxidation stateoxide selected from the group consisting of copper oxide, silver oxideand a combination thereof. In further embodiments, the single oxidationstate oxide is copper oxide. In still further embodiments, the materialcomprises a single oxidation state oxide selected from the groupconsisting of Cu₂O, CuO and combinations thereof. Each possibilityrepresents a separate embodiment of the invention. In certainembodiments, copper oxide is Cu₂O.

According to some embodiments, the metal oxides useful in the materialsof the present invention are selected from the group consisting ofcopper oxide, tetracopper tetroxide, silver oxide, tetrasilvertetroxide, zinc oxide and combinations thereof. According to furtherembodiments, the metal oxides are selected from the group consisting ofCu₂O, CuO, Cu₄O₄, Ag₂O, AgO, Ag₂O₃, Ag₄O₄, ZnO₂ and combinationsthereof. In particular embodiments, the material comprises at least twometal oxides selected from the group consisting of copper oxide,tetrasilver tetroxide, tetracopper tetroxide and combinations thereof.In the currently preferred embodiments, the single oxidation state oxideis copper oxide and the mixed oxidation state oxide is tetrasilvertetroxide. In further embodiments, the single oxidation state oxide iscuprous oxide and the mixed oxidation state oxide is tetrasilvertetroxide.

Combinations of copper oxide and zinc oxide are not known to providesynergistic antimicrobial effect. While acceleration of theantimicrobial effects of a naturally occurring copper oxide comprising amixture of cupric and cuprous oxides was disclosed, for example, in U.S.Pat. No. 7,169,402, the present invention provides for the first timenon-naturally occurring combinations of metal oxides, specificallycombinations comprising a single oxidation state oxide combined withtetracopper tetroxide or tetrasilver tetroxide, such combinations beingcharacterized by synergistic antimicrobial proliferation properties. Thesynergistic effect of the compositions comprising a mixture of twodifferent metal oxides, wherein at least one of the metal oxides is amixed oxidation state oxide is even more surprising considering thebiocidal activity of a combination of copper oxide and proven effectivesilver compound AlphaSan®, which was tested by the inventor of thepresent invention and presented in the experimental section. Addition ofthe silver compound AlphaSan® to Cu₂O did not increase the biocidal ratethereof and no synergistic acceleration was observed. Only when a mixedoxidation state form of either silver (Ag₄O₄) was combined with a singleoxidation state metal oxide comprising copper oxide, the antimicrobialproperties of the single oxidation state metal oxide were enhanced. Saidantimicrobial activity of the combination of the metal oxides wasincreased also as compared to the activity of the mixed oxidation statemetal alone. Without wishing to being bound by theory or mechanism ofaction, the measured synergistic effect of such combinations can beattributed to intervalence charge transfer between the metal ions havingdifferent oxidation states. Exposure of the combination of the at leasttwo metal oxides, comprising a mixed oxidation state oxide and a singleoxidation state oxide, to a mutual moisture reservoir establishes ioniccontact between the metal oxides and allows ion release from each metaloxide to the mutual moisture reservoir, thus providing acceleration ofmicrobial mortality rates.

According to further embodiments, the material of the present inventioncomprises a synergistic combination of at least two metal oxidesaccording to the principles of the present invention, wherein each ofthe metal oxides can be present in the combination at a weight percentof from about 0.05% to about 99.95%, such as from about 0.1% to about99.9%, or from about 0.5% to about 99.5%. Each possibility represents aseparate embodiment of the invention.

It has been surprisingly found that incorporation of a combination of amixed oxidation state oxide and a single oxidation state oxide into apolymer, wherein the mixed oxidation state oxide is present in a weightpercent of less than 10% in the total weight of the combination of themetal oxides was sufficient to cause the acceleration of antimicrobialactivity of said polymer, as compared to each of the polymers comprisingmixed oxidation state oxide and single oxidation state oxide alone. Thiswas even more surprising since the total weight of the mixed oxidationstate oxide in the polymer comprising the combination of the metal oxidepowders was ten times lower than in the polymer comprising the mixedoxidation state alone.

Thus, according to some embodiments, the mixed oxidation state oxideconstitutes from about 1% to about 20% wt. of the total weight of thecombination of the two metal oxides. According to yet furtherembodiments, the mixed oxidation state oxide constitutes from about 5%to about 15% wt. of the total weight of the combination of the two metaloxides. According to still further embodiments, the mixed oxidationstate oxide constitutes about 10% wt. of the total weight of thecombination of the two metal oxides.

According to other embodiments, the mixed oxidation state oxideconstitutes up to about 60% wt. of the total weight of the combinationof the two metal oxides, such as up to about 50% wt., up to about 40%wt., up to about 30% wt., up to about 20% wt. or up to about 15% wt. ofthe total weight of the combination of the two metal oxides. Eachpossibility represents a separate embodiment of the invention.

It has been further discovered that a polymer comprising as low as 3%wt. of the mixed oxidation state oxide in the metal oxides combinationhad increased biocidal activity as compared to the polymer comprisingthe single oxidation state oxide alone at the same weight percent of themetal oxide in the polymer as the weight percent of the metal oxidescombination. It was also surprisingly found that antimicrobial activityof the material comprising a combination of the two metal oxides wasenhanced as compared to the biocidal activity of single oxidation stateoxide, even when the combination comprised as low 0.5% wt. of the mixedoxidation state oxide. Therefore, the mixed oxidation state oxide canbeneficially be used in the material in a relatively low concentration,as compared to the single oxidation state oxide, thereby increasingcommercial viability of the material.

According to some embodiments, the mixed oxidation state oxideconstitutes from about 0.05% to about 99.5% wt. of the total weight ofthe combination of the two metal oxides, such as from about 0.05% toabout 90% wt., from about 0.05% to about 80% wt., from about 0.05% toabout 70% wt., from about 0.05% to about 60% wt., from about 0.05% toabout 50% wt., from about 0.05% to about 40% wt., from about 0.05% toabout 30% wt., from about 0.05% to about 20% wt., or from about 0.05% toabout 15% wt. of the total weight of the combination of the two metaloxides. Each possibility represents a separate embodiment of theinvention.

According to further embodiments, the mixed oxidation state oxideconstitutes from about 0.05% to about 15% wt. of the total weight of thecombination of the two metal oxides, such as from about 0.1% to about15% wt., from about 0.5% to about 15% wt., from about 1% to about 5%wt., from about 0.5% to about 5% wt., or from about 0.1% to about 3% wt.of the total weight of the combination of the two metal oxides. Eachpossibility represents a separate embodiment of the invention.

According to particular embodiments, the mixed oxidation state oxideconstitutes about 1% wt. of the total weight of the combination of thetwo metal oxides. According to further particular embodiments, the mixedoxidation state oxide constitutes about 0.5% wt. of the total weight ofthe combination of the two metal oxides. According to still furtherparticular embodiments, the mixed oxidation state oxide constitutesabout 0.1% wt. of the total weight of the combination of the two metaloxides. According to yet further particular embodiments, the mixedoxidation state oxide constitutes about 0.05% wt. of the total weight ofthe combination of the two metal oxides. According to some embodiments,the antimicrobial effect of the combination of the two metal oxides issynergistic.

According to some embodiments, the mixed oxidation state oxide ispresent in the synergistic combination of the metal oxide powders in adetectable amount. The presence of the mixed oxidation state oxide inthe synergistic mixture can be detected by means of an X-ray diffractionspectroscopy (XRD), electron microscopy, electron spectroscopy, Ramanspectroscopy or electoanalytical methods. Electron spectroscopyincludes, inter alia, X-ray photoelectron spectroscopy (XPS), electronspectroscopy for chemical analysis (ESCA and Auger electron spectroscopy(AES). The non-limiting example of electron microscopy method suitablefor the detection of mixed oxidation state oxide is Scanning electronmicroscopy (SEM), optionally conjugated with Energy-dispersive X-rayspectroscopy (EDS). According to certain embodiments, the presence ofthe mixed oxidation state oxide is detected by XRD.

The Metal Oxide Powders

The copper oxide useful in the materials of the present invention can beany commercially available copper oxide powder with a purity level of noless than 97% wt. In some exemplary embodiments, the powder is purchasedfrom SCM Inc. of North Carolina, USA. Due to the prevalence of suppliersof this powder it is not economically viable to manufacture the powder.The zinc oxide useful in the materials of the present invention can beany commercially available zinc oxide powder with a recommended puritylevel of no less than 98% wt. which is readily available commercially.However, due to the difficulty in obtaining tetrasilver tetroxide and/ortetracopper tetroxide, it is necessary to synthesize the specificspecies as described hereinbelow.

According to some embodiments, the particle size of the commerciallyavailable metal oxide powder is from about 10 to about 20 micron. Themetal oxide powder can be ground to a particle size of from about 1nanometer to about 10 micron. Accordingly, the size of the metal oxideparticles in the materials of the present invention can be from about 1nanometer to about 10 microns. According to some embodiments, theparticle size is from about 1 to 10 micron. According to furtherembodiments, the particle size is from about 5 to about 8 micron.According to other further embodiments, the particle size is from about0.1 to about 0.5 micron. According to further embodiments, the particlesize is from about 0.25 to about 0.35 micron According to someembodiments, the metal oxide powders comprise agglomerates which are nolarger than 20 microns. According to other embodiments, the metal oxidepowders comprise agglomerates which are no larger than 10 microns. Inother embodiments, the materials of the present invention are devoid ofmetal oxide particles agglomerates.

The Polymer

As used herein, the term “polymer” or “polymeric” refers to materialsconsisting of repeated building blocks called monomers. The polymer maybe homogenous or heterogeneous in its form; hydrophilic or hydrophobic;natural, synthetic, mixed synthetic or bioplastic. The non-limitingexamples of polymers suitable for incorporation of the metal oxidepowders include, inter alia, polyamide, polyester, acrylic, isotacticcompounds including but not limited to polypropylene, polyethylene,polyolefin, acrylic compounds, polyalkene, silicones, and nitrile;cellulose-based polymer or a mixture of different cellulose materials;converted cellulose mixed with plasticizers such as but not limited torayon viscose, starch-based polymer, and acetate; petroleum derivativesand petroleum gels; fats, both synthetic and natural; polyurethane;natural latex; and mixtures and combinations thereof. Each possibilityrepresents a separate embodiment of the invention.

According to some embodiments, the polymer is a synthetic polymer,including organic polymers, inorganic polymers and bioplastics.According to some embodiments, the polymer is selected from the groupconsisting of polyamide, polyester, acrylic, polyolefin, polysiloxane,nitrile, polyvinyl acetate, cellulose-based polymers, starch-basedpolymer, derivatives, dispersions and combinations thereof. Eachpossibility represents a separate embodiment of the invention. Thenon-limiting examples of the cellulose-based polymer are viscose orrayon. According to certain embodiments, the polymer is selected fromthe group consisting of polyamide, polyester, acrylic, polyalkene andcombinations thereof. According to other embodiments, the polymer isselected from the group consisting of polyamide, polyalkene,polyurethane, polyester and combinations thereof. Each possibilityrepresents a separate embodiment of the invention. According toparticular embodiments, the polymer is selected from polyethylene,polypropylene, acrylonitrile butadiene styrene (ABS), polylactic acid(PLA), polyglycolic acid (PGA), poly(lactic-co-glycolic acid) (PLGA),poly(butyl acrylate) (PBA), polybutylene terephthalate (PBT) andcombinations thereof. The polymer may be water based or solvent based.

Combinations of more than one of said materials can also be usedprovided they are compatible or adjusted for compatibility.

The Polymer Having the Metal Oxide Powders Incorporated Therein

According to some embodiments, the metal oxide powders are incorporatedinto the polymer by a master batch manufacturing.

As used herein, the term “master batch” unless otherwise indicated,refers to a carrier polymer containing metal oxide particles, formedinto pellets or granules, wherein the polymer is compatible with the endproduct material. The master batch can be added as a chemical additiveto a polymeric slurry comprising same or chemically compatible polymerbefore extrusion, molding, casting or 3D printing. Alternatively, themaster batch can comprise a compounded resin containing the final dosageof the polymers and the metal oxides required for the product to beformed from the polymer.

Metal oxide powders can be included in a polymer using a master batchsystem so that the powder particles form part of the entire polymericproduct. However, the currently known processes for the preparation of apolymeric material having antimicrobial properties are adapted forinclusion of a single type of metal oxide. The present inventionprovides materials comprising a combination of a mixed oxidation stateoxide of a first metal and a single oxidation state oxide of a secondmetal. According to some exemplary embodiments, the first metal and thesecond metal are different. Thus, according to further embodiments, theat least two metal oxide powders have substantially different specificgravities.

When two or more particulate compounds having different specificgravities and being disruptive to non-isotactic materials, such as themajority of polymers, have to be incorporated into the polymericmaterial, control over suspension and dispersion of the particles in thepolymeric slurry is complicated. Such slurries generally yieldinhomogeneous extruded or cast polymers. Dispersion and suspension ofdistinct metal oxide powders is not usually practiced in master batchproduction, where normally a specific single compound is desired to beadded to the polymer. Therefore, when reducing the invention topractice, it was required to develop a method allowing incorporation ofat least two metal oxide powders having substantially different specificgravities into a polymer fiber. Furthermore, since the amount of anymetal oxide powder that can be incorporated into a polymer is limited bythe disruption effect of the metal oxide on cross polymerization ofnon-isotactic polymers or weakening of the carrier polymer, it wasnecessary to develop a method to accommodate a high amount of multiplemetal oxides in these polymers. The present invention thus provides aprocess for the preparation of the material having antimicrobialproperties, providing control over the metal oxide particlesconcentration and distribution in the polymer. The present inventionfurther provides materials having antimicrobial properties, comprising acombination of at least two metal oxide powders, wherein the metal oxidepowders are incorporated within the polymer fiber in a generally uniformfashion. As used herein, the terms “generally uniform” or “homogeneous”that can be used interchangeably, denote that the volume percentage ofthe metal oxide particles on the polymer surface or in the bulk thereofvaries by less than 20%, preferably less than 10%.

According to some embodiments, the materials of the present inventioncomprise at least two metal oxide powders having substantially differentspecific gravities. “Substantially different specific gravity” refers,in another embodiment, to the variance in the specific gravities of theat least two metal oxide powders, which is higher than about 5%. Inanother embodiment, the term refers to the variance of higher than about10%. In yet another embodiment, the term refers to the variance ofhigher than about 15%.

To accommodate a plurality of metal oxide powders having distinctspecific gravities in a single polymeric slurry, it is necessary tocompensate for the particle weight differences of the metal oxides. Inorder to do so, the bulk densities of the metal oxide powders should beequalized. As used herein, the term “bulk density” refers to the mass ofmany particles of the powder divided by the total volume they occupy.According to some embodiments, the material comprises at least two metaloxides powders processed to have a substantially similar bulk density.“Substantially similar bulk density” refers, in some embodiments, to thevariance in the bulk density of the at least two metal oxide powders,which is less than about 20%. In another embodiment, the term refers tothe variance of less than about 10%. In yet another embodiment, the termrefers to the variance of less than about 5%.

For example, specific gravity of copper oxide is 6.0 g/ml, whereinspecific gravity of tetrasilver tetroxide is 7.48 g/ml. The bulkdensities of the unprocessed copper oxide and the tetrasilver tetroxidepowders are thus significantly different. Without wishing to being boundby theory or mechanism of action, in order to be incorporated into thepolymer in a substantially uniform manner, the powders have to beprocessed to equalize the bulk densities thereof. Equalizing the bulkdensities of the metal oxide powders can be achieved by altering theparticle size of the metal oxide powders. Said particle size alterationcan be performed by decreasing or increasing the particle size of thepowders. For example, the particles size of the powders can be decreasedby grinding and increased by applying a coating. The extent of theincrease or decrease in the particle sizes of one metal oxide powder ascompared to the other metal oxide powder is dependent on the specificgravities and/or the initial bulk densities of said metal oxide powders.

According to some embodiments, the metal oxide powders are processed bygrinding. In other embodiments, the metal oxide powders are processed bymilling. According to certain embodiments, the metal oxide powders areprocessed to have mean particle sizes which are inversely proportionalto the specific gravities thereof. According to another embodiment, themetal oxide powders are ground to have mean particle sizes which areinversely proportional to the specific gravities thereof. According tothe further embodiments, the mean particle sizes of the metal oxidepowders are inversely proportional to the specific gravity thereof.

According to further embodiments, the material comprises at least twometal oxide powders having essentially similar particle sizes.“Substantially similar particle size” refers, in another embodiment, tothe variance in the particle size of the at least two metal oxidepowders which is less than about 20%. In another embodiment, the termrefers to the variance of less than about 10%. In yet anotherembodiment, the term refers to the variance of less than about 5%. Instill another embodiment, the term refers to the variance of less thanabout 1%.

According to further embodiments, the metal oxide powders are processedto have substantially similar particle sizes. According to furtherembodiments, the metal oxide powders are ground to have substantiallysimilar particle sizes. According to yet further embodiments, at leastone of the metal oxide powders is ground to obtain the at least twometal powders having substantially similar particle sizes.

According to some embodiments, the particles of at least one metal oxidepowder comprise a coating. According to other embodiments, the particlesof at least two metal oxide powders comprise the coating. In someembodiments, at least one of the metal oxide powders is processed tohave coated particles. In further embodiments, each of the at least twometal oxide powders is processed to have coated particles. According tocertain embodiments, said particles have substantially similar sizes.According to further embodiments, the coating thickness is proportionalto the specific gravity of the metal oxide powders. According to yetfurther embodiments, the coating weight is proportional to the specificgravity of the metal oxide powders. According to some embodiments, theat least two metal oxide powders comprise particles having a differentcoating material. The molecular or specific weight of the coatingmaterial can be adjusted to compensate for the difference in thespecific gravities of the metal oxide powders.

The metal oxide particles coating may comprise polyester or polyalkenewax. The non-limiting examples of the polyalkene wax includepolypropylene wax marketed by Clariant as Licowax PP 230, an oxidizedpolyethylene wax marketed by Clariant as Licowax PED 521, an oxidizedpolyethylene wax marketed by Clariant as Licowax PED 121 or an ethylenehomopolymer wax marketed by BASF as Luwax®.

According to further embodiments, the coating material comprises acopolymer of polyethylene wax and maleic anhydride. According to yetfurther embodiments, the coating material further comprises ionomers oflow molecular weight waxes. According to additional embodiments, thepolyethylene wax has a high wettability. In some embodiments, thecoating material comprises homopolymers, oxidized homopolymers, highdensity oxidized homopolymers and co-polymers of polyethylene,polypropylene and ionomer waxes, micronized polyalkene waxes or mixturesthereof, as well as co-polymers of ethylene-acrylic acid andethylene-vinyl acetate.

A critical prerequisite for the usability of such an additiveconcentrate is the correct choice of the wax component. Although it isnot colored itself, it influences the performance of the additiveconcentrate. For more detailed information, reference may be made, forexample, to the product brochure “Luwaxe®—Anwendung inPigmentkonzentraten” about polyethylene waxes from BASF AG.

According to some embodiments, the weight of the coating materialapplied to the powder constitutes from about 0.2% to about 2% wt. of themetal oxide powder weight. According to additional embodiments, theweight of the coating material constitutes from about 0.2% to about 1%wt. of the metal oxide powder weight, preferably from about 0.4 to about0.5% wt. Each possibility represents a separate embodiment of theinvention. In a certain embodiment, the weight of the coating materialconstitutes about 1% wt. of the metal oxide powder weight.

According to other embodiments, the first metal and the second metal arethe same. According to further embodiments, the at least two metalpowders have substantially similar bulk densities.

Without wishing to being bound by theory or mechanism of action, inorder to hinder a chemical interaction between the metal oxide powdersand the carrier polymer or the polymer fiber, the metal oxides should bepretreated with an encapsulating compound. Said compounds isolate themetal oxides so that they will not interact with the polymeric materialand are configured to abrade off the powder during product use. Thus,according to some embodiments, the materials of the present inventioncomprise metal oxide powders, comprising particles encapsulated withinan encapsulating compound. The encapsulating compound can be selectedfrom the group consisting of silicates, acrylates, cellulose,protein-based compounds, peptide-based compounds, derivatives andcombinations thereof. In some embodiments, the encapsulating compound isselected from the group consisting of silicate, poly(methylmethacrylate) (PMMA) and a combination thereof.

According to some embodiments, the weight of the encapsulating compoundapplied to the powder constitutes from about 0.2% to about 2% wt. of themetal oxide powder weight. According to additional embodiments, theweight of the encapsulating compound constitutes from about 0.2% toabout 1% wt. of the metal oxide powder weight, preferably from about 0.4to about 0.5% wt. Each possibility represents a separate embodiment ofthe invention.

Additionally or alternatively, the chemical interaction between themetal oxide powders and the carrier polymer or the polymeric support,can be hindered through addition of metal deactivating agents orchelating agents. As used herein, the terms “metal deactivating agents”and “chelating agents” that can be used interchangeably, refer to anagent generally comprising organic molecules containing heteroatoms orfunctional groups such as a hydroxyl or carboxyl, the agent acting bychelation of the metal to form inactive or stable complexes.

Thus, according to some embodiments, the materials of the presentinvention comprise a metal deactivating agent or a chelating agent. Infurther embodiments, the materials of the present invention comprise ametal deactivating agent or a chelating agent associated with the metaloxide powders. The non-limiting example of the said metal deactivatingagents and/or chelating agents include a phenolic antioxidant, potassiumiodide, potassium bromide, calcium stearate, zinc stearate, aluminumstearate, tertiary chain extenders and combinations thereof. Accordingto a particular embodiment, the metal deactivating agent is a phenolicantioxidant. The phenolic antioxidant can be selected from, but notlimited to 2′,3-bis [[3-[3,5-di-tert-butyl-4-hydroxyphenyl] propionyl]]propionohydrazide marketed under the name Irganox® MD 1024 by CIBA;Vitamin E (alpha-tocopherol) which is a high molecular weight phenolicantioxidant, marketed under the name Irganox E 201 by CIBA; Irganox B1171, marketed by CIBA, which is a blend of a hindered phenolicantioxidant and a phosphate; and combination thereof. According tocertain embodiments, the metal deactivating agents abrade off the metaloxide particles upon hydration of the material.

According to some embodiments, the weight of the metal deactivatingagent applied to the powders constitutes from about 0.2% to about 5% wt.of the metal oxide powder weight. According to additional embodiments,the weight of the metal deactivating agent comprises from about 0.5% toabout 1% wt. of the metal oxide powder weight. In a certain embodiment,the weight of the metal deactivating agent constitutes about 1% wt. ofthe metal oxide powder weight.

Another difficulty in adding almost any inorganic compound to apolymeric material is particle agglomeration. According to someembodiments, the metal oxide particles of the present invention aretreated by a surfactant to prevent metal oxide particles agglomeration.Therefore, according to some embodiments, the materials of the presentinvention comprise a surfactant. In further embodiments, the materialscomprise a surfactant associated with the metal oxide powders. Thenon-limiting examples of the surfactant include but are not limited toSigma Aldrich Niaproof®, Dow Corning Xiameter® and Triton-X-100.

According to some embodiments, the weight of the surfactant constitutesfrom about 0.05% to about 2% wt. of the metal oxide powder weight. In acertain embodiment, the weight of the surfactant constitutes about 0.5%wt. of the metal oxide powder weight.

According to some embodiments, the metal oxide powders are present inthe master batch at a weigh percent of from about 0.5% to about 95% ofthe total weigh of the master batch. According to further embodiments,the metal oxide powders are present in the master batch at a weighpercent of from about 5% to about 50%, preferably from about 20% toabout 40%. Each possibility represents a separate embodiment of theinvention. According to some embodiments, the master batch is preparedfor direct extrusion, molding or casting, without further mixing with anadditional polymer. In certain such embodiments, the metal oxide powdersare present in the master batch at a weigh percent of from about 0.5% toabout 30% of the total weigh of the master batch, preferably from about0.5% to about 15% of the total weigh of the master batch. According tofurther embodiments, the metal oxide powders are present in the masterbatch in an amount configured to provide from about 0.5% wt. to about30% wt. of the metal oxide particles in the material obtained through amaster batch manufacture process, preferably from about 0.5% wt. toabout 15% wt., or from about 1% wt. to about 5% wt. of the metal oxidesof the total weight of the material. Each possibility represents aseparate embodiment of the invention.

The composition of the master batch, comprising the polymer and thesynergistic composition of the metal oxides can be formed into asemi-final or a final product. The semi-final product may include, interalia, a fiber, a yarn, a textile, a fabric, a film or a foil; and thefinal product may include, inter alia a textile product or a non-textilepolymeric article. According to some embodiments, the fiber is apolymeric fiber, being synthetic or semi-synthetic. The fiber may be astaple fiber or a filament fiber. According to some embodiments, themaster batch composition is formed into a semi-final or final product bymeans of extrusion, molding, casting or 3D printing of the polymer,comprising said synergistic combination. According to furtherembodiments, the material is selected from an extruded, molded, cast or3D printed polymer. Each possibility represents a separate embodiment ofthe invention.

Thus, in some embodiments, the metal oxide powders are present in themaster batch in an amount configured to provide from about 0.5% to about30% wt. of the metal oxide particles in the extruded or molded polymerobtained through a master batch manufacture process, preferably fromabout 0.5% wt. to about 15% wt., or from about 1% wt. to about 5% wt. ofthe metal oxides of the total weight of the extruded or molded polymer.Each possibility represents a separate embodiment of the invention. Instill further embodiments, the metal oxide powders are present in themaster batch in an amount configured to provide from about 0.5% to about30% wt. of the metal oxide particles in the polymer fiber obtainedthrough a master batch manufacture process, preferably from about 0.5%wt. to about 15% wt., or from about 1% wt. to about 5% wt. of the metaloxides of the total weight of the total weight of the polymer fiber.Each possibility represents a separate embodiment of the invention.

In some embodiments, the combined weight of the at least two metaloxides constitutes from about 0.25% to about 50% wt. of the total weighof the materials.

In some embodiments, the material is in a form of a semi-final product,selected from a fiber, a yarn, a textile, a fabric, a film or a foil. Incertain such embodiments, the combined weight of the at least two metaloxides constitutes from about 0.5% to about 30% wt. of the total weightof the semi-final product.

According to further embodiments, the combined weight of the at leasttwo metal oxides constitutes from about 1% to about 15% wt. of the totalweight of the semi-final product. In certain such embodiments, thepolymer is selected from polyester or polyamide. In further embodiments,the semi-final product is a fiber, preferably including a staple fiber.According to certain embodiments, the combined weight of the at leasttwo metal oxides constitutes from about 1% to about 5% wt. of the totalweight of the semi-final product. According to other embodiments, thecombined weight of the at least two metal oxides constitutes from about3% to about 8% wt. of the total weight of the semi-final product.

According to further embodiments, the combined weight of the at leasttwo metal oxides constitutes from about 0.5% to about 8% wt. of thetotal weight of the semi-final product. In certain such embodiments, thepolymer is selected from polyester or polyamide. In further embodiments,the semi-final product is a fiber, preferably including a filamentfiber. According to certain embodiments, the combined weight of the atleast two metal oxides constitutes from about 1% to about 4% wt. of thetotal weight of the semi-final product. According to other embodiments,the combined weight of the at least two metal oxides constitutes fromabout 0.5% to about 2% wt. of the total weight of the semi-finalproduct.

According to further embodiments, the combined weight of the at leasttwo metal oxides constitutes from about 10% to about 30% wt. of thetotal weight of the semi-final product. In certain such embodiments, thepolymer is a polyalkene. In further embodiments, the semi-final productis a fiber.

In some embodiments, the combined weight of the at least two metal oxidepowders constitutes from about 3% to about 8% wt. of the total weight ofmaterial and the size of the metal oxide particles is from about 0.5 toabout 1 micron. In particular embodiments, the combined weight of the atleast two metal oxide powders constitutes about 3% wt. of the totalweight of material, wherein the metal oxide particles size is about 1micron. In other embodiments, the combined weight of the metal oxidespowders constitutes about 8% wt. of the total weight of material,wherein the metal oxide particles size is about 0.5 micron.

In some embodiments, the polymer fiber is blended with a natural fiber.The natural fiber may be selected from the group consisting of cotton,silk, wool, linen and combinations thereof. In additional embodiments,the material further comprises a modified cellulose fiber. Thenon-limiting examples of cellulose modified fiber include viscose andrayon.

According to some embodiments, the natural fiber may be present in thematerial in a weight percent of up to about 95% of the total weight ofthe material. In further embodiments, the material of the presentinvention comprises from about 50% to about 85% wt. of natural fiber.According to some exemplary embodiment, the natural fiber may be presentin the material in a weight percent of about 70% of the total weight ofthe material. According to further embodiments, the weight ratio betweenthe polymer fiber with at least two metal powders incorporated thereinand the natural fiber is from about 1:1 to about 1:6. The blend materialtherefore may comprise from about 50% wt. natural fiber/50% wt. polymerfiber to about 85% wt. natural fiber/15% wt. polymer fiber. In certainembodiments, the material comprises from about 50% wt. cotton/50% wt.polymer fiber to about 85% wt. cotton/15% wt. polymer fiber.

According to some embodiments, the material comprises a semi-finalproduct comprising to blend of a polymeric fiber and a natural fiber. Incertain such embodiments, the combined weight of the at least two metaloxides constitutes from about 0.25% to about 5% wt. of the total weightof the semi-final product.

In some embodiments, the material comprises 100% wt. polymer fiber withat least two metal powders incorporated therein. Therefore, the materialof the present invention can be devoid of natural fibers.

According to some embodiments, the weight of the mixed oxidation stateoxide constitutes from about 0.001% to about 30% wt. of the total weightof the material. In some embodiments, the mixed oxidation state metaloxide constitutes from about 0.05% to about 2.5% wt. of the total weightof the material, preferably from about 0.1% to about 1% wt. of the totalweight of the material. Each possibility represents a separateembodiment of the invention. The material can be selected from anintermediate, semi-final and final material.

According to some embodiments, the material having antimicrobialproperties comprises the polymer and a synergistic combination of the atleast two metal oxide powders, wherein the powders are incorporatedwithin the polymer. According to some embodiments, the metal oxidespowders are attached to the polymer. According to further embodiments,the powders are attached to the polymer surface. According to otherembodiments, the powders are embedded into the polymer. According tofurther embodiments, the powders are embedded into the polymer surface.According to other embodiments, the powders are deposited on the polymersurface. According to additional embodiments, the powders are insertedinto the polymer. According to further embodiments, the powders areinserted into the polymer surface. According to further embodiments, themetal oxide powders particles protrude from the polymer surface.According to still further embodiments, at least part of the metal oxidepowders particles protrudes from the polymer surface. According to someembodiments, at least 10% of the synergistic combination of the metaloxides is present on the surface of the polymer. According to furtherembodiments, at least 5% of the synergistic combination of the metaloxides is present on the surface of the polymer. It has been found thatas little as 1% appearance on the surface of a polymeric fiber, whichcontains particles protruding from the polymer surface, was sufficientto ensure a biocidal effect. Thus, according to some embodiments, atleast 1% of the synergistic combination of the metal oxides is presenton the surface of the polymer. According to other embodiments, thepowders are not exposed on the surface of the polymer. According to someembodiments, said polymer is an extruded, cast or molded polymer or isin a form of a polymer fiber, a textile product or a non-textilepolymeric article. Each possibility represents a separate embodiment ofthe invention.

The End Product

The materials of the present invention comprise a polymer and at leasttwo metal powders incorporated therein, wherein the polymer can be anextruded, molded, cast or 3D printed polymer. According to someembodiments, said polymer is a molded polymer. In other embodiments, thepolymer is an extruded polymer. In certain embodiments, the polymer is aform of a fiber. According to some embodiments, the fiber can be formedinto a yarn, textile or fabric. According to some embodiments, thetextile is selected from a woven textile, a knit textile, a non-woventextile, a needle-punch textile or felt.

According to certain embodiments, the final product includes amonolithic layer obtained by stacking of nano-denier fibers such asthose produced using an electro-spinning process, said fibers comprisingsaid synergistic combination of the metal oxide powders. In someembodiments, the metal oxide particles are disposed between thenano-fibers in the sheaths.

Also provided according to some embodiments of the present invention isan extruded polymer in the form of a staple or a filament fiber,comprising said metal oxide particles incorporated into a polymer fiberand formed as a non-extruded non-woven material or filling.

According to further embodiments, the semi-final product can be formedinto a final product.

According to some embodiments, final products of the present inventionhave a soft surface. The term “soft surface” as used herein, refers toall surfaces which are solid but are not hard surfaces, and most oftenrefers to products made from knit, woven, or non-woven textile products.The final products of the present invention include, but are not limitedto, textile products and non-textile polymeric articles.

The textile product may be selected from, but not limited to, clothingitems, bedding textiles, laboratory or hospital textiles, medicaltextiles including bandages or sutures and textiles for internal use,and personal hygiene articles. The non-limiting examples of the textileproducts include pillowcases, eye-masks, gloves, socks, stockings,sleeves, shoe covers, slippers, undergarments, industrial uniforms,sportswear, towels, kitchen cloths, lab coats, floor cloths, sheets,bedding, curtains, textile covers, hard surface covers, diapers,incontinence pads, feminine hygiene products, gauze pads, monolithicextruded membranes, body-suits, trans-dermal patches, bandages, adhesivebandages, sutures, sheaths and textiles for internal use, compressiongarments in all sizes for different parts of the body, and absorbentpads.

The non-textile polymeric article may be selected from, but not limitedto, packaging and wrapping material, laboratory equipment, hospitalequipment, preferably disposable hospital equipment, covers for consumeritems, food equipment, agricultural products, sanitary products orbirth-control devices. The non-limiting examples of the non-textilepolymeric articles include food packages, gloves, blood bags, catheters,ventilation tubes, feeding tubes, transmission tubes, covers for mobilephones, pipes, toilet seats or toilet seat covers, kitchen sponges,working surface covers, and condoms.

Products formed from the materials of the present invention, possesseffective antimicrobial properties, including, but not limited toantimicrobial, antibacterial, antiviral, anti-fungal, and anti-miteproperties.

Thus, according to some embodiments, the present invention provides thematerial for use in combating or inhibiting the activity of microbes ormicro-organisms, selected from the group consisting of gram-positivebacteria, gram-negative bacteria, fungi, parasites, mold, spores,yeasts, protozoa, algae, acarii and viruses. Each possibility representsa separate embodiment of the invention. According to some embodiments,the present invention provides a method for combating or inhibiting theactivity of microbes or micro-organisms, the method comprising providingto health care facilities the material according to the principles ofthe invention.

According to some embodiments, the material is for use in combatinghealthcare associated infections, nosocomial infections or a combinationthereof. According to some embodiments, the present invention provides amethod for combating healthcare associated infections, nosocomialinfections or a combination thereof, the method comprising providing tohealth care facilities the material according to the principles of theinvention.

The materials of the present invention can be particularly applicable incontrolling hospital acquired infections, odor reduction in garments,socks, stockings and underclothing, in wound healing articles such asgauze, wound coverings, disposable sanitary products, disposablediapers, and sutures, single use garments, diapers and articles ofclothing that can come in contact with a wound.

Alternatively or additionally, the material of the present invention canbe used for the treatment or prevention of atopic fungal, bacterial andviral infections. The infection may be selected from the groupconsisting of athlete's foot, yeast infections and staph infections. Infurther embodiments, the material is used for the treatment orprevention of topical viral infections. The infection may be selectedfrom the group consisting of warts and Herpes B. According to someembodiments, the present invention provides a method of treatment orprevention of atopic fungal, bacterial and viral infections, the methodcomprising topically applying to the body of the subject in need of suchtreatment the material according to the principles of the invention.

Thus, also provided according to the principles of the present inventionis a product, preferably a textile product, used for the control oftopical fungal infections, yeast infections and/or for topical viralcontrol. In some embodiments, the metal oxide powders incorporated intothe polymer may further be included in a film, fiber, textile patch andform that can be placed on the infected area, said form being selectedfrom the group consisting of socks, panties, underwear, sleeves andpatches. According to some embodiments, the metal oxide particles areincorporated into a fiber which is included in a substrate or textilemade from a film, a non-woven material or a textile substrate for use incombating dust mites.

Preparation Method

In another aspect, the present invention provides a method for thepreparation of the material according to the principles of the presentinvention, the method comprising the steps of:

a. processing the at least two metal oxide powders to have substantiallysimilar bulk densities; and

b. mixing said powders with at least one polymer.

According to some embodiments, step a. comprises processing the metaloxide powders to obtain particles having sizes which are inverselyproportional to the specific gravity thereof. According to someembodiments, step a. comprises reducing the metal oxide powders particlesize to obtain particles having sizes which are inversely proportionalto the specific gravity thereof. According to other embodiments, step a.comprises processing the metal oxide powders to obtain particles havingsubstantially similar sizes. According to other embodiments, step a.comprises reducing the metal oxide powders particle size to obtainparticles having substantially similar sizes. In some embodiments, saidprocessing comprises grinding.

In additional embodiments, step a. further comprises applying a coatingto the metal oxide powder particles. According to some embodiments, thecoating thickness is proportional to the specific gravity of the metaloxide particles. According to other embodiments, the coating weight isproportional to the specific gravity of the metal oxide particles.According to some embodiments, the coating is applied to metal oxidepowders having substantially similar particle sizes. According tofurther embodiments, the coating is applied to at least one metal oxidepowder. According to other embodiments, the coating is applied to atleast two metal oxide powders. According to further embodiments, thecoating comprises polyester or polyalkene wax. The polyester orpolyalkene wax may be selected from the group consisting of apolypropylene wax, oxidized polyethylene wax, ethylene homopolymer wax,and different types of waxes including copolymers of polyethylene waxand maleic anhydride which can also be used with ionomers of lowmolecular weight waxes or any combination thereof.

In some embodiments, the method further comprises a step ofencapsulating the metal oxide powder particles within an encapsulatingcompound. In other embodiments, the method comprises a step of mixingthe metal oxide powders with a metal deactivating agent or a chelatingagent. In further embodiments, the method comprises a step of mixing themetal oxide powders with a surfactant. In some embodiments, theadditional steps are performed prior to mixing the metal oxide powderswith the polymer.

The encapsulating compound may be selected from the group consisting ofsilicate, acrylate, cellulose, derivatives thereof and combinationsthereof. The metal deactivating agent may be selected from the groupconsisting of phenolic antioxidant, potassium iodide, potassium bromide,calcium stearate, zinc stearate, aluminum stearate, tertiary chainextender and a combination thereof.

In additional embodiments, the method comprises preparing the mixedoxidation state oxide. The mixed oxidation state oxide can be preparedby a standard procedure, for example as described by Hammer andKleinberg in Inorganic Synthesis (IV,12) or in U.S. Pat. No. 5,336,416,which are incorporated by reference herein in their entirety. The methodmay further include a step of grinding the obtained mixed oxidationstate oxide powder.

According to some embodiments, the mixing of the metal oxide powders andthe at least one polymer is assisted by sonication. According to furtherembodiments, the metal oxide powders are mixed with a polymer fiber.According to still further embodiments, the metal oxide powders areembedded into the polymer fiber by means of sonication.

According to further embodiments, step b. comprises producing a masterbatch, comprising the metal oxide powders and a carrier polymer.According to some embodiments, said at least one polymer comprises thecarrier polymer. According to the preferred embodiments, the masterbatch is homogeneous. According to additional embodiments, the metaloxide powders are distributed in the master batch in a generally uniformmanner. The master batch may be formed into pellets. Alternatively, themaster batch may be formed into granules. The carrier polymer may beselected from the group consisting of polyamide, polyalkene,polyurethane, polyester and combinations thereof.

In some embodiments step b. further comprises adding the master batch toa polymer slurry. In further embodiments the polymer slurry comprises apolymer, which is the same as the carrier polymer. In other embodiments,the polymer slurry comprises a polymer, which is chemically compatiblewith the carrier polymer. In some embodiments, the polymer is selectedfrom the group consisting of polyamide, polyalkene, polyurethane andpolyester. Combinations of more than one of said materials can also beused provided they are compatible or adjusted for compatibility. Thepolymeric raw materials are usually in bead form and can bemono-component, bi-component or multi-component in nature. The beads areheated to melting at a temperature which preferably will range fromabout 120° C. to 180° C. for isotactic polymers and up to 270° C. forpolyester. The master batch is then added to the polymer slurry andallowed to spread through the heated slurry. The particle size of themetal oxide powders in these embodiments is preferably between 1 and 5microns. However particulate size can be larger when the film or fiberthickness can accommodate larger particles.

According to some embodiments, the metal oxides are incorporateddirectly into the polymer fiber. According to further embodiments,particle size of the metal oxide powders is between 0.1 and 0.5 microns.According to still further embodiments, incorporation of the metal oxidepowders into the polymer fiber is assisted by sonication.

According to some embodiments, the method further comprises step c.comprising forming from the obtained mixture a semi-final or a finalproduct. Thus, in some embodiments, the method further comprises step c.comprising forming from the obtained mixture a film, a foil, a fiber, ayarn, a fiber or a textile, comprising said powders. Each possibilityrepresents a separate embodiment of the invention. According to furtherembodiments, the method comprises a step of forming the film, foil,fiber, yarn, fiber or textile into a textile product or a non-textilepolymeric article.

In some embodiments, step c. comprises extrusion, molding, casting or 3Dprinting of the mixture obtained in step b. In some exemplaryembodiments step c. comprises extrusion. In certain such embodiments,the polymer slurry is transferred to an extrusion tank. In furtherembodiments, the liquid polymer slurry is pushed through holes in aseries of metal plates formed into a circle called a spinneret. Thepolymer slurry is pushed through a spinneret by applying pressure on theslurry. As the slurry is pushed through the fine holes that are closetogether, they form single fibers or if allowed to contact one another,they form a film or sheath. The hot liquid fiber or film is pushedupwards, cooled with cold air, forming a continuous series of fibers ora circular sheet. The thickness of the fibers or sheet is controlled bythe size of the holes and speed at which the slurry is pushed throughthe holes and upward by the cooling air flow. In the preferredembodiments, the fibers are homogeneously extruded.

In some embodiments, step c. comprises forming a polymeric fiber fromthe mixture obtained in step b. The formation of a fiber can be ineither filament form (continuous) or staple form (short cut). In bothcases an amount of master batch is added to the hot polymeric slurry toyield the final amount of the combination of the at least two metaloxide powders desired for the end product. By way of example if a 1%final load is desired in a filament fiber than 50 kilo of a 20% wt.concentrated master batch will be added to complete 1 ton of totalslurry. By way of example if a 3% final load is desired in a staplefiber than 150 kilo of a 20% wt. concentrated master batch will be addedto complete 1 ton of total slurry. In both cases, after a thoroughmixing of the concentrated master batch in the slurry tub to obtain goodmaster batch dispersion, the extruded fibers will contain the desiredamount of the metal oxides combination.

In a normal process as known to those familiar with the art, the activeingredient will be evenly dispersed and remain in suspension of thepolymeric slurry. If the master batch is not prepared correctly then themetal oxides will interact with the target polymer and disrupt thelinkage process thus inhibiting the formation of a solid fiber. Inaddition, if the wax is not applied correctly the metal oxides willeither sink to the bottom of the mixing tub and block the holes of thespinneret or will remain floating at the top of the slurry and not getmixed into the fibers. Normally extrusion is done using gravity so thatthe weight of the slurry in the tub pushes the polymer through thespinneret holes. The polymer is designed to solidify with exposure toair. Once the fibers are exposed to air they are wound on bobbins forfurther processing.

According to some embodiments, the fiber is selected from the groupconsisting of a staple fiber, a filament fiber and a combinationthereof. According to some embodiments, the polymer fiber is a syntheticor a semi-synthetic fiber. According to further embodiments, thesynthetic or semi-synthetic fiber is selected from the group consistingof polyolefin fibers, polyurethane fibers, vinyl fibers, nylon fibers,polyester fibers, acrylic fibers, cellulose fibers, regenerated proteinfibers, blends and combinations thereof. In some embodiments, the methodfurther comprises blending the polymer fiber with a natural fiber.According to further embodiments, the natural fibers are selected fromthe group consisting of cotton, silk, wool, linen and combinationsthereof.

According to further embodiments, the method includes forming thepolymer fiber into a yarn. According to some embodiments, the yarn is asynthetic yarn or a combination of the synthetic yarn with a naturalyarn. In some embodiments, the synthetic yarn is spun from saidsynthetic fibers. According to further embodiments, the yarn is formedinto fabrics. According to further embodiments, the fabrics are woven,knit or non-woven.

In additional embodiments the method further comprises forming thematerial into a textile product or a non-textile polymeric article.According to further embodiments, step c. comprises directly formingfrom the mixture obtained in step b. a textile product or a non-textilepolymeric article. Each possibility represents a separate embodiment ofthe invention. In certain such embodiments, step c includes molding,casting or extruding the mixture obtained in step b. into a desiredshape or form. In certain embodiments, step c. comprises applying themixture of the metal oxide powders with the at least one polymer,obtained in step b. to a pre-formed polymer article as a second layer.In some embodiments, the polymer is latex, nitrile or an artificialrubber.

The following examples are presented for illustrative purposes only andare to be construed as non-limitative to the scope of the invention.

EXAMPLES Example 1: Mixed Oxidation State Oxide Powder Preparation

A tetrasilver tetroxide powder was prepared through a reduction processfrom a silver nitrate solution by a standard procedure known to a personskilled in the art, and as described by Hammer and Kleinberg inInorganic Synthesis (volume IV, page 12). It should be further notedthat the powder obtained by the described process should be very softand capable of being converted into a nano-powder with a relative ease.

The basic tetrasilver tetroxide (Ag₄O₄) synthesis as referenced abovewas prepared by addition of NaOH into distilled water, followed byaddition of a potassium persulfate and then the addition of silvernitrate.

A tetracopper tetroxide powder can be prepared using copper sulfate andpotassium persulfate as an oxidizing agent, as described in U.S. Pat.No. 5,336,416 to Antelman. However, for the sake of commercial viabilitycuprous oxide was purchased and used as a starting material to obtainCu₄O₄ according to the described procedure.

The particle size of both powders received varies from nano-particles toagglomerated particles as large as 20 microns.

These powders can be ground down to the desired particle size and mixedeither together or with copper oxide or zinc oxide. The copper oxideused in the development is a cuprous oxide (brown/red) with a puritylevel of no less than 97% in a 10-20 μm size particle. In this case, thepowder was purchased from SCM Inc. of North Carolina, USA, but can bepurchased from any supplier who can furnish this purity level. Thepowder is then ground down to 1 to 5 μm. Due to the prevalence ofsuppliers of this powder it is not economically viable to manufacturethe powder. However, due to the difficulty in obtaining tetrasilvertetroxide and/or tetracopper tetroxide, it is necessary to synthesizethe specific species as described hereinabove.

Example 2: Master Batch Preparation

The metal oxides were incorporated into a polymer using a master batchsystem so that the powder is embedded on the outside of the polymer andforms part of the entire polymeric product.

To accommodate the different specific gravities of more than one metaloxide in a common master batch, it is necessary to compensate for thedifferences between the two different metals, should a difference intheir weight exist. This is done using two systems as described:

In the first system, the particle sizes of each metal oxide were madeequal through proportional size equalization. The specific gravity ofcopper oxide is approximately 6 g/ml and the specific gravity oftetrasilver tetroxide is 7.48 g/ml. Tetrasilver tetroxide particles wereground down to be approximately 10% to 15% smaller than the copper oxideparticles.

In the second system, the particles were all ground to the same size butthe heavier particles were coated with a higher amount of polyester waxor polyethylene wax.

The wax was applied in a high sheer mixer in a weight/weight ratio ofapproximately 10 grams wax to 1000 grams metal oxide. It was found thata higher amount of polyester wax on the heavier metal oxide aids inmaintaining the suspension of the metal oxide in the polymer slurry. Thewetting capability of the waxes should also be good. To isolate themetal oxide from a chemical interaction with the carrier polymer, themetal oxide powders were pretreated with an encapsulating compound. Theinert encapsulating compounds used were a silicate and Poly(methylmethacrylate) (PMMA). The encapsulation was performed in a high sheermixer in a weight/weight ratio of approximately 4 g encapsulating agentto 1000 g metal oxide powder.

Example 3: Polymer and Blended Polymer Fiber and Yarn Preparation

The fabrication of a polymeric yarn having antimicrobial properties,characterized by a protrusion of the metal oxide particles on thesurface of the polymer in both a filament and staple product isdescribed.

It should be noted that for the sake of this example, tetrasilvertetroxide and/or tetracopper tetroxide and/or copper oxide were used butthat the proportions for using other metal oxides compounds are the sameapproximate proportions.

A description of the general production process of fibers is as follows:

1. Slurry is prepared from any polymer, the chief raw materialpreferably being selected from polyamide, polyalkene, polyurethane andpolyester. Combinations of more than one of said materials can also beused provided they are compatible or adjusted for compatibility. Thepolymeric raw materials are usually in bead form and can bemono-component, bi-component or multi-component in nature. The beads areheated to melting at a temperature which preferably will range fromabout 120 to 180° C. for isotactic polymers and up to 270° C. forpolyester.

2. At the hot mixing stage, before extrusion, a water insoluble powderof the chosen metal oxide compounds in the form of master batch is addedto the slurry and allowed to spread through the heated slurry. Theparticulate size will be preferably between 1 and 5 microns, howeverparticulate size can be larger when the film or fiber thickness canaccommodate larger particles.

3. The liquid slurry is then pushed with pressure through holes in aseries of metal plates formed into a circle called a spinneret. As theslurry is pushed through the fine holes that are close together, theyform single fibers or if allowed to contact one another, they form afilm or sheath. The hot liquid fiber or film is pushed upwards, cooledwith cold air, forming a continuous series of fibers or a circularsheet. The thickness of the fibers or sheet is controlled by the size ofthe holes and speed at which the slurry is pushed through the holes andupward by the cooling air flow.

Filament Fiber

It is noted that the specific gravity of each metal oxide is differentand therefore required a treatment of a different coating compound orapplying different amount of the same coating compound so that bothmetal oxide powders would be homogeneously dispersed in the liquidpolyester slurry. The metal oxide particles were mixed with the carrierand formed into pellets. As it relates to filament fiber this produces atotal of 50 kilo of master batch which is a total of the copper oxideand/or the tetrasilver and/or tetracopper tetroxide is together. Theproportion of the carrier to active material was 5:1 yielding a 20% wt.concentration of the metal oxides in the master batch. 50 kilo of themaster batch were mixed into an extrusion tank for spinning through aspinneret and were sufficient to produce 1 ton of a filament polymericyarn yielding a total of a 1% final concentration of the two metaloxides (active material) together in the polymer yarn. It should benoted that if the particles are below 0.5 microns in size it was foundthat the loading of the metal oxides in a filament fiber can beincreased to as much as 4% wt.

Staple Fiber

For the production of a staple fiber, 28.5 kilo of copper oxide havingparticle size ground to 1 to 5 microns and 1.5 kilo of tetrasilvertetroxide ground to 1 to 5 microns were mixed with 120 kilo of thechosen carrier polyester polymer for the creation of a master batch. Thespecific gravity of each compound was different and therefore required acoating by a different coating compound, such as Clariant Licowax PP230and BASF Luwax® or by different amounts of said compounds, such that themetal oxide particles would be homogeneously dispersed in thesuspension. The compounds were mixed with the carrier and were formedinto pellets. This produced a total of 150 kilo of master batch. The 150kilo of master batch was mixed into an extrusion tank for spinningthrough a spinneret and was sufficient to produce 1 ton of a polymericstaple yarn yielding a total of a 3% wt. final concentration of the twocompounds in the polymer fiber.

FIGS. 1A-1C present Scanning Electron Microscope (SEM) micrographs of apolyester staple fiber having a combination of copper oxide andtetrasilver tetroxide powders incorporated within. The polymer fiber wasprepared by a master batch process as described hereinabove. It can beseen that the metal oxide particles are uniformly distributed on thesurface of the polymer fiber. It can also be seen that the metal oxideparticles of the synergistic combination protrude from the surface ofsaid polymer fiber.

As a comparative study, FIGS. 2A and 2B represent a cotton fibercomprising sonochemically deposited copper oxide and further impregnatedwith tetrasilver tetroxide. The larger particles are tetrasilvertetroxide particles and the smaller particles are copper oxideparticles.

It has been further found that the load level in a polyolefin fiber canbe much higher than in a polyester or nylon fiber due to the isotacticnature of the olefins. While load levels as discussed above were limitedto 1% wt. in filament fibers and 3% wt. in staple fibers, it was foundthat as much as 20% wt. could be added to polypropylene fibers.

Staple and filament fiber combined with cotton.

A master batch was created as described hereinabove, using polyesterresins to which 20 wt. of a mixture comprising copper oxide and TST wasadded. Both the copper oxide and the TST were about 98% pure. The metaloxide composition comprised 99.5% copper oxide and 0.5% wt. TST. Themaster batch was then added to a polyester slurry being in a liquid formin a proportion that yielded a final loading of copper oxide of about 3%wt. in the final fiber. The copper oxide in the sample was 97.7% purewith 2.3% being impurities. The fibers were extruded in the same manneras normal staple polyester fibers and were then blended with cotton sothat the final load of treated fibers is a total of 30% wt. copper oxideand TST impregnated fibers/70% cotton in a 24/1 s forming a ring spuncombed cotton yarn twisted for weaving. The yarns were then knit into afabric that weighs 150 grams to the square meter.

It should be noted that in the mixtures comprising up to 10% by weightof the metal oxide, no degradation of the physical properties wasobserved. As described hereinbelow, the materials having as low as 0.5%wt. of the metal oxides combination demonstrated limited efficacy inantimicrobial properties, as well as surprising inhibition of HIV-1activity.

Example 4: Preparation of Staple Fiber Having Encapsulated Metal OxidePowders

A polyester staple fiber was prepared by combining copper oxide powderwhich constituted 2.85% wt. of the total weight of the fiber andtetrasilver tetroxide powder which constituted 0.015% wt. of the totalweigh of the fiber. The particle size of the metal oxides was broughtdown to between 0.25 to 0.35 microns and the powders were incorporateddirectly into the polymer fiber. The process included milling thepowders to the desired size, placing the powders on the fiber andpassing the fiber with the powders through a trough of water thoughwhich ultrasonic waves were passed.

FIG. 3 shows SEM micrograph of the fibers obtained via said process,wherein the copper oxide and TST particles are under the surface whichappear as unclear white spots in the SEM micrograph. Particles on thefibers surface in the photographs were evaluated by a spectrographicreading and found not to be copper oxide or TST but rather a combinationof complex organic groups which are the polymer itself.

Example 5: Polymer Yarn Preparation Through a Standard Extrusion Process

The same procedure as in Example 3 was followed for the preparation ofthe master batch but the yarn was obtained through a procedure involvingstandard film extrusion equipment. The viscosity of the slurry wascontrolled through the master batch flow rates, by a procedure which isknown to those familiar with the art.

Example 6: Molded Polymer Preparation

The powders and the master batch including the combined powdersincluding copper oxide and TST, and polypropylene were prepared asdescribed hereinabove. The master batch has to accommodate the carrierpolymeric slurry into which it will be added. In molded and/or castproducts the master batch concentration can be any amount up to andincluding 40% active ingredient however, amounts of 20% to 25% would bepreferred so as to avoid possible problems in the chemical dispersion inthe slurry. The master batch was allowed to melt in the polymeric slurryuntil the slurry was homogenous. No temperature changes were made. Thepolymeric slurry is then cast into a desired form or extruded to producea product of a particular shape. The polypropylene slurry was extrudedinto a polypropylene film having copper oxide and TST incorporatedtherein.

Example 7: Cellulose-Based Polymer Yarn Preparation

A rayon slurry or any cellulose slurry (waste of cotton and corn arevery popular as a source of cellulose) is mixed with a plasticizer as isknown in the industry of the production of these types of fibers.Normally the process involves a number of chemical steps that involvethe breaking down of cellulose to very fine mulch of individual cells,adding a plasticizer, and then exposing the slurry to a solidifyingprocess.

A powder made up of a combination of the two metal oxides, includingcopper oxide and tetrasilver tetroxide, was prepared. The metal powderswere thoroughly mixed together and ground down to a particulate size ofpreferably under 5 μm.

The powder was then added to the cellulose based slurry in a ratio of upto 3% wt. of the powder to the total weight of the slurry. The powderwas added exactly at the same time the slurry is being passed throughthe holes of the spinneret so that the exposure to the acid in the finalstep of the process is limited to a few seconds as is common in the waythese fibers are made.

The resulting slurry was solidified such that the metal oxide particlesare homogeneously impregnated throughout the fiber.

Example 8: Latex Glove Preparation

A natural latex slurry is prepared using the accepted amount of latexsolids and water and other compounds. In the case of a glove there isusually between 20% and 35% latex solids. The slurry is heated and aglove mold is dipped into the liquid and removed. The excess latex isallowed to drip off the glove which is still on the mold, thus creatinga thin layer of latex on the mold. The latex and mold are then placed inan oven which cures the latex at the temperatures needed to cause thecross linking of the material. This first curing of the latex convertsthe liquid latex to a latex solid. The latex layer is allowed to coolbut will remain sticky until it is dried through a second exposure todry heat. After the first curing the latex is cross linked and now hasthe form of a flexible film in molded form but is still in a stickystate.

While the latex on the mold is still sticky but solid, and before thesecond exposure to heat, a second bath is prepared. The mold and thesticky latex are dipped in a latex slurry for a second time. The secondbath is also a latex slurry but contains as much as but not limited to5% wt. latex solids and 0.25% wt. of a copper oxide and TST mixture.This amount of copper oxide and TST was found to be sufficient for theantimicrobial and antiviral effect. When the sticky molded glove wasdipped in the diluted latex copper oxide and TST bath a very thincolored coating was created which could be seen on the glove. At thisstage it was also found that a pigment could be added to the slurry tochange the color of the glove if so desired.

The particle size of the copper oxide and the TST in the system wasmeasured to be approximately 5 μm but this procedure can be performedwith both smaller and larger particles. Preferably, the copper oxideparticles protrude from the surface of the latex.

It should be noted that the second latex dip acts only as a binder tothe copper oxide, and binds excellently to the latex below the layer,allowing for the exposed copper oxide and TST mixture to be bound to thelatex without any negative weakening of the latex glove. The mold withthe two layers of latex is cured a second time and is run through adrying process. There was no need for another curing of the outer layerdue to its low thickness.

Example 9: Antimicrobial Properties of the Metal Oxides

This example contains several experiments performed to test theantimicrobial properties of the combination of the single oxidationstate and mixed oxidation state oxides.

Test 1: Antiviral Properties

100 μl aliquots of freshly prepared HIV-1 were incubated on top of thefibers produced according to the procedure described in Example 3, withvarying amounts and ratios of copper oxide and tetrasilver tetroxide, aspresented in Table 1. The incubation was performed for 30 minutes at 37°C. Then 10 μl of each incubated virus solution were added to MT-2 cells(human lymphocyte cell line) cultured in 1 ml neutral medium. The cellswere then incubated for 5 days in a moist incubator at 37° C. and thevirus proliferation was determined by measuring the amount of p24 (HIV-1capsid protein) in the supernatant with a commercial ELISA (enzymelinked immunesorbent assay) kit. The results show the average ofduplicate experiments. As control for possible cytotoxicity of the Ag₄O₄in combination with copper oxide to the cells, similar experiments werecarried out as above. The fibers were incubated with 100 μl ofstandard/control medium that did not contain HIV-1. No cytotoxicity wasobserved.

Table 1 summarizes the evaluation of the ability of the fiberscontaining a combination of Ag₄O₄ and copper oxide, to inhibit HIV-1proliferation in tissue culture, as compared to the fibers, containingcopper oxide or tetrasilver tetroxide alone and to fibers, which do notcontain metal oxides.

TABLE 1 Anti-viral efficacy test results. Test # Polymeric Fiber activematerial Inhibition (%) 1 Control - no anti-viral agent 0 2 With 1% wt.Cu₂O 70 3 With 1% wt. TST 76 4 With 0.1% wt. TST/1% wt. Cu₂O 96

Test 2: Anti-Bacterial, Anti-Fungal and Anti-Mite Properties.

Extruded polypropylene films containing a combination of copper oxideand TST were used to test antibacterial properties of the extrudedpolymer comprising a synergistic combination of the metal oxides. Thefilms were prepared as described in Example 5. In all cases, the mixedoxidation state oxide—tetrasilver tetroxide and the single oxidationstate oxide—copper oxide together constituted 3% wt. of the total weightof the extruded film. The mixture of the metal oxides comprised 3% wt.TST and 97% wt. copper oxide. As a control, a polypropylene filmcontaining a single oxidation state oxide as a sole active ingredientwas tested so that levels of microbial inhibition could be observed. Asa control for combined metal oxides activity, a polypropylene film wasextruded with a copper oxide and an elemental silver ceramic compoundtypically used as a silver-based antimicrobial material, thus providinga polymer having a combination of two single oxidation state oxides. Thecombined weight of copper oxide and the silver ceramic compound powdersconstituted 3% wt. of the total weight of the extruded film. Thecombined powders comprised 3% wt. silver (AlphaSan® silver basedantimicrobial additive from Milliken, Inc. of the USA) and 97% copperoxide.

Polymer fibers combined with cotton, containing a combination of copperoxide and TST were used to test dust-mites biocidal properties of thefibers comprising a synergistic combination of the metal oxides. Thepolymer/cotton blend fibers were prepared as described in Example 3. Themetal oxide composition comprised 99.5% copper oxide and 0.5% wt. TST.The blended fibers included 30% wt. copper oxide and TST impregnatedfibers and 70% cotton. As a control, a 70% polymer/30% cotton blendfibers containing a single oxidation state oxide as a sole activeingredient were used. The positive control was made exactly as thecombination copper oxide and TST but without the TST so that the activeingredient was 100% copper oxide. The negative control was again madethe same as the two other fibers but with no active ingredient.

The American Association of Textile Chemists and Colorist (AATCC) TestMethod 100 was used to determine the biocidal properties of the filmsagainst the bacteria and fungi tested. The initial bacterial or fungalinoculum used varied between 1×10⁵ and 4×10⁶ colony forming units (CFU)per ml. However, in an attempt to see the pure effect of the metaloxides, the sample film used in these tests which contained the bacteriawere diluted using a saline solution so that growth medium was highlydiluted and removed from the films and bacterial proliferation wassignificantly reduced when incubated at 25° C. and 70% relativehumidity.

Measurements of the micro-organism levels were performed at 5 minuteintervals for biocidal activity evaluation of every film towards each ofthe micro-organisms. The time recorded below relates to the timerequired to achieve a kill rate, which provides a 99% reduction (a 2-logreduction) in the micro-organism levels.

The tested antibacterial properties of the material, which includes acombination of two single oxidation state oxides instead of acombination of a mixed oxidation state oxide and a single oxidationstate oxide, as compared to such properties of a single oxidation stateoxide alone, are presented in Table 2. The tested antibacterial,antiviral and anti-mite properties of the materials comprising acombination of a mixed oxidation state oxide and a single oxidationstate oxide, as compared to such properties of a single oxidation stateoxide alone, are presented in Table 3. The tested antibacterialproperties of the polypropylene extruded film, which includes acombination of copper oxide and TST, as compared to a control, which isthe same fiber without any active ingredient, are presented in FIG. 4.

Other than the final test in Table 3 (dust mites), times were measuredat 5 minute intervals until the 99% reduction in the micro-organismlevels was reached. All tests were done in triplicates and the resultsin the table represent an average. In the final test (dust mites on 70%cotton, 30% polyester), times were measured at 24 hour intervals untilthe 99% reduction in the micro-organism levels was reached.

As can be seen from Table 2, addition of AlphaSan® to copper oxide didnot reduce the time required for a 2-log reduction by the polypropylenefilm containing AlphaSan® and copper oxide. In contrast, Table 3 showsthat polymer films and fibers including a combination of tetrasilvertetroxide (silver in the form of mixed oxidation state) and copper oxidehad higher biocidal activity that films and fibers containing copperoxide alone, as expressed by shorter times required to achieve the 2-logreduction.

TABLE 2 Antibacterial properties of the polumeric material, whichincludes a combination of two single oxidation state oxides. Cu₂OCu₂O/AlphaSan ® Micro-organism Time Reduction Time Reduction tested[min] [%] [min] [%] S. aureus (Gram+) 60 99.8 60 99.7 (Staphylococcus)E. coli (Gram−) 55 99.5 60 99.6

TABLE 3 Antibacterial, antiviral and anti-mite properties of thematerials comprising a combination of a mixed oxidation state oxide anda single oxidation state oxide. Cu₂O Cu₂O/TST Polymeric ReductionReduction Material Organism Tested Time [%] Time [%] S. aureus 60 Min.99.8 15 Min. 99.7 E. coli 55 Min. 99.5 15 Min. 99.6 C. albicans 120 Min.99.9 25 Min. 99.5 (Candida) L. monocytogenes, 60 Min. 99.8 15 Min. 99.3Gram+ (Listeria) S. enterica, 110 Min. 99.0 25 Min. 99.2 Gram−(Salmonella) 70% Cotton/ Dust mites * 5 days 100 3 days 100 30%Polyester (Dermatophagoides) Fabric * 100 Dust Mites were placed on thefilm with food and placed in an incubator at 37° C. at 70% relativehumidity. Mortality rates were counted once a day.

Example 10: Proliferation Inhibition Testing on Polymer Fabrics UsingAATCC Test Method 100-2004

The previous set of experiments (Example 9) simulated a scenario wherebacteria reside on a film which is not being worn by a person. Hence,the experimental conditions were set up to follow such scenario(incubation with no added nutrients, at room temperature).

The current experiment deals with a more realistic situation in whichthe fabric is worn in close proximity by a person. The human body actsas a reservoir and constantly supplies moisture, heat, and nutrients tomicroorganisms residing on the fabric via perspiration. Therefore, theincubation of bacteria on the fabric was carried out in 37° C. and withnutrients, as per AATCC Test Method 100-2004.

Two types of samples were prepared. One type (regular copper oxidefabrics) included fabrics containing 3% wt. copper oxide in a polyesterfiber. Another type (accelerated copper oxide fabrics) contained 2.4%wt. copper oxide+TST, of which copper oxide constituted 99.5% wt. andTST constituted 0.5% wt. in the same size polyester fiber as the fiberabove.

All fabrics were sterilized prior to use via submergence in ethanol 70%for 10 minutes, followed by overnight drying in a sterile environment.Bacteria (E. coli) were grown overnight in a LB medium (10% tryptone 5%yeast extract, 10% NaCl (wt. %)) and diluted to approximately 10⁵ CFU/mlwith a fresh autoclaved LB medium. The treated fabrics and the controlswere then soaked with 1 ml of the bacteria containing medium, placed ina closed sterile jar and incubated at 37° C. for the specified times.

Bacteria were extracted from the fabrics using fresh LB medium and then200 μl were seeded on LB-agar petri dishes overnight to allow the growthof colonies.

The effective reduction of the population of bacteria on each fabric wascompared to its own control untreated fabric of the same material weaveand size. Each experiment was done in duplicate, and averaged. The testresults are presented in Tables 4-6.

TABLE 4 Effective reduction of the population of bacteria by applyingfabrics comprising a single oxidation state oxide or a combination of amixed oxidation state oxide and a single oxidation state oxide measuredat the time period of 0-40 min Copper oxide + TST Copper oxide Time(min) Treated Untreated Reduction Treated Untreated Reduction 0 80,000145,000 44.82% 85,000 87,500 NR 20 127,500 215,000 40.69% 235,000145,000 −62.01% 40 80,000 210,000 61.90% 150,000 130,000 −15.38%

TABLE 5 Effective reduction of the population of bacteria by applyingfabrics comprising a single oxidation state oxide or a combination of amixed oxidation state oxide and a single oxidation state oxide measuredat the time period of 0-180 min Copper oxide + TST Copper oxide Time(min) Treated Untreated Reduction Treated Untreated Reduction 0 87,500162,500 46.15% 107,500 122,500 NR 60 172,500 280,000 38.39% 82,500307,500 73.17% 180 240,000 2,150,000 88.83% 2,200,000 2,347,500 6.28%

TABLE 6 Effective reduction of the population of bacteria by applyingfabrics comprising a combination of a mixed oxidation state oxide and asingle oxidation state oxide measured at the time period of 0-300 minCopper oxide + TST Time (min) Treated Untreated Reduction 0 82,50060,000 NR 180 87,500 632,500 86.16% 300 1,335,000 4,300,000 68.95%

The bacteria proliferation inhibiting properties of the tested fabricsare also presented in FIGS. 5A-5C and 6A-6B.

The results show that the fabric treated with copper oxide and TST ismore effective in inhibition of bacterial growth as compared to copperoxide alone, especially in the longer timescales of higher than 180 min.

Example 11: Proliferation Inhibition Testing on Blended Polymer-CottonFabrics Using AATCC Test Method 100-2004

Two types of samples were prepared. One type (regular copper oxidefabrics) included a combination of polyester and cotton fibers, whereinthe polymer fiber contained 3% wt. copper oxide relatively to the totalweight of the polymer fiber. The copper oxide in the sample was 97.7%pure with 2.3% being impurities. The fibers were extruded in the samemanner as normal staple polyester fibers and were then blended withcotton so that the final load of treated fibers is 30% copper oxideimpregnated fibers/70% cotton in a 24/1 s forming a ring spun combedcotton yarn twisted for weaving. The yarns were then knit into a fabricthat weighs 150 grams to the square meter.

Another type (accelerated copper oxide fabrics) included a combinationof polyester and cotton fibers, wherein the polymer fiber is impregnatedwith 3% wt. copper oxide+TST, of which copper oxide constituted 99.5%wt. and TST constituted 0.5% wt. The fibers were extruded in the samemanner as normal staple polyester fibers and were then blended withcotton so that the final load of treated fibers is a total of 30% copperoxide and TST accelerator impregnated fibers/70% cotton in a 24/1 sforming a ring spun combed cotton yarn twisted for weaving. The yarnswere then knit into a fabric that weighs 150 grams to the square meter.

The two types of samples were tested using AATCC Test Method 100-2004(Quantitative), as described in Example 10, against a control fabric.The control comprised 30% untreated polyester/70% cotton fabrics with aweight of approximately 150 grams to the square meter. No fabrics weredyed. All fabrics were sterilized prior to use via submergence inethanol 70% for 10 minutes, followed by overnight drying in a sterileenvironment.

The results of the bacterial proliferation inhibition test are presentedin FIG. 7. It was clearly shown that the polymer-cotton blend fabricscomprising a combination of a mixed oxidation state oxide and a singleoxidation state oxide have higher antimicrobial activity as compared tothe same fabrics comprising single oxidation state oxide alone.

Example 12: Detection of the Mixed Oxidation State Oxide in the PolymerMaterial

A portion of textiles or fibers or molded or cast product is put in anoven and brought to a temperature which allows the polymer to becarbonized to dust, but which is below the melting temperature of themetal oxides. The dust is then placed in an X-Ray Diffraction systemwhich identifies crystalline structure of a crystal and as such candetect the presence of the metal oxides powders in the sample, which arepresent in addition to the carbon dust.

While the present invention has been particularly described, personsskilled in the art will appreciate that many variations andmodifications can be made. Therefore, the invention is not to beconstrued as restricted to the particularly described embodiments,rather the scope, spirit and concept of the invention will be morereadily understood by reference to the claims which follow.

1. A method of treating a wound, comprising applying to the wound amaterial having antimicrobial properties, said material comprising asynergistic combination of at least two metal oxide powders, comprisinga mixed oxidation state oxide of a first metal and a single oxidationstate oxide of a second metal, wherein the mixed oxidation state oxideconstitutes from about 0.05% to about 15% wt. of the total weight of thesynergistic combination of the at least two metal oxide powders andwherein the ions of the metal oxides are in ionic contact upon exposureof said material to moisture.
 2. The method according to claim 1,wherein the mixed oxidation state oxide is selected from the groupconsisting of tetrasilver tetroxide (Ag₄O₄), Ag₂O₂, tetracoppertetroxide (Cu₄O₄), Cu (I,III) oxide, Cu (II,III) oxide and combinationsthereof and wherein the single oxidation state oxide is selected fromthe group consisting of copper oxide, silver oxide, zinc oxide andcombinations thereof.
 3. The method according to claim 2, wherein thesynergistic combination of the at least two metal oxide powderscomprises copper oxide and tetrasilver tetroxide.
 4. The methodaccording to claim 1, wherein each of the metal oxide powdersindependently comprises particles, which size is from about 10nanometers to about 10 microns.
 5. The method according to claim 1,wherein the metal oxide powders comprise particles encapsulated withinan encapsulating compound being selected from the group consisting ofsilicates, acrylates, cellulose, protein-based compounds, peptide-basedcompounds, derivatives and combinations thereof.
 6. The method accordingto claim 1, wherein the material comprises a polymeric material havingincorporated therein the synergistic combination of at least two metaloxide powders.
 7. The material according to claim 6, wherein the polymeris selected from the group consisting of polyamide, polyester, acrylic,polyalkene, polysiloxane, nitrile, polyvinyl acetate, starch-basedpolymer, cellulose-based polymer, dispersions and mixtures thereof. 8.The method according to claim 1, wherein the material is incorporatedinto a wound healing article, selected from the group consisting of agauze, gauze pad, wound covering, trans-dermal patch, bandage, adhesivebandage disposable sanitary product, suture, and article of clothingthat can come in contact with a wound.
 9. A wound healing articlecomprising a material having antimicrobial properties, said materialcomprising a synergistic combination of at least two metal oxidepowders, comprising a mixed oxidation state oxide of a first metal and asingle oxidation state oxide of a second metal, wherein the mixedoxidation state oxide constitutes from about 0.05% to about 15% wt. ofthe total weight of the synergistic combination of the at least twometal oxide powders and wherein the ions of the metal oxides are inionic contact upon exposure of said material to moisture.
 10. The woundhealing article according to claim 9, being in a form selected from thegroup consisting of a gauze, gauze pad, wound covering, trans-dermalpatch, bandage, adhesive bandage disposable sanitary product, suture,and article of clothing that can come in contact with a wound.
 11. Thewound healing article according to claim 9, wherein the mixed oxidationstate oxide is selected from the group consisting of tetrasilvertetroxide (Ag₄O₄), Ag₂O₂, tetracopper tetroxide (Cu₄O₄), Cu (I,III)oxide, Cu oxide and combinations thereof and wherein the singleoxidation state oxide is selected from the group consisting of copperoxide, silver oxide, zinc oxide and combinations thereof.
 12. The woundhealing article according to claim 11, wherein the synergisticcombination of the at least two metal oxide powders comprises copperoxide and tetrasilver tetroxide.
 13. The wound healing article accordingto claim 9, wherein each of the metal oxide powders independentlycomprises particles, which size is from about 10 nanometers to about 10microns.
 14. The wound healing article according to claim 9, wherein themetal oxide powders comprise particles encapsulated within anencapsulating compound.
 15. The wound healing article according to claim14, wherein the encapsulating compound is selected from the groupconsisting of silicates, acrylates, cellulose, protein-based compounds,peptide-based compounds, derivatives and combinations thereof.
 16. Thewound healing article according to claim 15, wherein the weight of theencapsulating compound applied to the powder constitutes from about 0.2%to about 2% wt. of the metal oxide powders weight.
 17. The wound healingarticle according to claim 9, wherein the material comprises a polymericmaterial having incorporated therein the synergistic combination of atleast two metal oxide powders.
 18. The wound healing article accordingto claim 17, wherein the metal oxide powders have substantiallydifferent specific gravities and substantially similar bulk densities,wherein the metal oxide powders comprise particles which mean particlesize is inversely proportional to the specific gravity thereof orwherein the metal oxide powders comprise particles which havesubstantially similar mean particles sizes and wherein said particlesare coated with a coating, which thickness is proportional to thespecific gravity of the metal oxide particles.
 19. The wound healingarticle according to claim 17, wherein the polymer is selected from thegroup consisting of polyamide, polyester, acrylic, polyalkene,polysiloxane, nitrile, polyvinyl acetate, starch-based polymer,cellulose-based polymer, dispersions and mixtures thereof.
 20. The woundhealing article according to claim 17, further comprising a naturalfiber, selected from the group consisting of cotton, silk, wool, linenand combinations thereof.